6-ketoprostaglandin-f1-alpha and Body-Weight

This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment. Etoricoxib and celecoxib had no effect on the urinary thromboxane metabolite, 11-dehydrothromboxane B(2), while significantly decreasing the urinary prostacyclin metabolite, 2,3-dinor-6-keto PGF(1alpha). Decreases were greater for both metabolites following naproxen. Ambulatory systolic blood pressures were significantly higher than placebo for all treatments, with moderately greater increases for etoricoxib relative to other active treatments on day 14. Ambulatory diastolic blood pressures were significantly higher than placebo for etoricoxib and naproxen but not for celecoxib.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Celecoxib; Constipation; Creatinine; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Electrolytes; Etoricoxib; Female; Headache; Humans; Male; Middle Aged; Naproxen; Potassium; Prostaglandins; Pyrazoles; Pyridines; Sodium; Sulfonamides; Sulfones; Thromboxane B2

In addition to a variety of lipids, 2 products of the arachidonic acid cascade, prostacyclin and thromboxane, are involved in the pathogenesis of atherosclerosis as a result of their effects on platelet function and on the vascular endothelium. The aim of the present investigation was to ascertain if a sub-maximal 8 week endurance training period followed by a 4 week detraining period would have any effects on high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), 2,3-dinor-6-keto-prostaglandin F(1alpha) (2,3-dinor-6-keto-PGF(1alpha)), the urinary metabolite of prostacyclin, 2,3-dinor-thromboxane B2 (2,3-dinor-TXB2), the urinary metabolite of thromboxane, and the ratios of TC to HDL-C and of 2,3 dinor-6-keto-PGF(1alpha) to 2,3-dinor-TXB2. Thirty-eight boys aged 10-14 were randomly divided into exercise (n = 21) and control (n = 17) groups. The exercise group trained on a bicycle ergometer 4 times/week, 1 h/session, at 80% of their physical working capacity at a heart rate of 170 beats/min (PWC(170)), for 8 weeks. The control group did not participate in any specific physical exercise program. The results showed that relative to the control group, the exercise group had a significant increase in HDL-C and 2,3-dinor-6-keto-PGF(1alpha) concentrations at the end of the 4th (p < 0.05 and p < 0.001, respectively) and the 8th week (p < 0.01 and p < 0.001) of training, respectively; a significant increase in the 2,3 dinor-6-keto-PGF(1alpha) - 2,3-dinor-TXB2 ratio (p < 0.05 and p < 0.01 at the same intervals); a significant decrease in TG at the end of the 8th week of training (p < 0.05); and a significant decrease in the TC--HDL-C ratio at the end of the 4th (p < 0.05) and 8th weeks of training (p < 0.001).

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Arachidonic Acid; Body Weight; Child; Cholesterol; Cholesterol, HDL; Heart Rate; Humans; Lipids; Longitudinal Studies; Male; Physical Endurance; Physical Exertion; Physical Fitness; Thromboxane B2; Triglycerides

The renin-angiotensin system plays a critical role in cardiovascular function, but little is known about the effects of specific cyclooxygenase 2 (COX-2) inhibition on this system in healthy humans under physiologic conditions.. Twenty-one healthy female volunteers received, in a randomized, double-blind, crossover study, celecoxib 200 mg twice a day, indomethacin 50 mg three times a day, or placebo for 4 days and a single dose, each, on day 5. On day 5 of each treatment, the following parameters were assessed with subjects in an upright position before and after administration of 20 mg furosemide intravenously: plasma renin activity (PRA), plasma aldosterone, serum and urine electrolytes, and creatinine. Index metabolites of prostanoids were analyzed by gas chromatography-tandem mass spectrometry in 24-hour urine on day 4 and in 2-hour urines before and after furosemide administration.. Baseline and furosemide-stimulated PRA were reduced to a similar degree by celecoxib and indomethacin. Plasma aldosterone and urinary excretion of potassium showed changes consistent with the alteration of PRA. Urinary excretion rates of prostaglandin E(2), (PGE(2)), 7alpha-hydroxy-5, 11-diketotetranor-prosta-1,16-dioic acid (PGE-M), and 2,3-dinor-thromboxane B(2) (TxB(2)) were not reduced by celecoxib, whereas indomethacin led to a decrease of 40%, 45%, and 80%, respectively. Both active treatments inhibited urinary excretion of 2,3-dinor-6-keto-PGF(1alpha) and 6-keto-PGF(1alpha) by 60% and 40%, respectively.. Renin-release in healthy humans with normal salt intake is COX-2 dependent. While COX-1 is critical for renal and systemic PGE(2) production, renal prostacyclin synthesis is apparently COX-2 dependent. Finally, the previously demonstrated shift of the thromboxane-prostacyclin balance toward prothrombotic thromboxane by specific COX-2 inhibition is confirmed.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aldosterone; Body Weight; Celecoxib; Creatinine; Cross-Over Studies; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Diuretics; Female; Furosemide; Humans; Indomethacin; Kidney; Potassium; Prostaglandins; Pyrazoles; Renin; Sodium; Sulfonamides; Thromboxane B2

The present study investigated whether the nitric oxide (NO) system is involved in cyclosporin A (CsA)-induced changes in cardiovascular and renal function in man.. Ten healthy volunteers were investigated twice--with and without intake of a single dose of CsA (8 mg/kg). N(G)-monomethyl-L-arginine (L-NMMA; 3 mg/kg) was injected 4 h after study start on each day.. There was no change in glomerular filtration rate (GFR) on the day without CsA. CsA alone did not change GFR, but after L-NMMA injection, GFR decreased significantly from 101 +/- 4 to 91 +/- 4 ml/min. L-NMMA increased renal vascular resistance with no difference between the two study days. CsA increased significantly the diastolic blood pressure (BP) by 8 +/- 2% and the heart rate (HR) by 30 +/- 4%, without changes in cardiac output L-NMMA further increased BP by around 8%, and decreased HR by 11% and cardiac output by 20% on both study days. L-NMMA decreased urinary flow rate by around 25% and renal sodium clearance from 1.1 to approximately 0.6 ml/min on both study days. CsA decreased plasma renin significantly and increased the urinary excretion rate of prostaglandin E2 (PgE2), 6-keto-prostaglandin F1alpha (6-keto-PgF1alpha) and thromboxane B2(TxB2) when compared to the control day. The urinary excretion rate of NOx and cGMP declined gradually on the control day. In contrast, there was a minor, non-significant increase in NOx and cGMP excretion after CsA, followed by a decrease (29 +/- 2 and 16 +/- 4%, respectively) after L-NMMA in parallel with the decrease in GFR.. The present findings suggest that NO does not play a major role during acute CsA-induced changes in cardiovascular function and renal haemodynamics in man. Renal NO synthesis, however, may attenuate the acute CsA-induced decrease in GFR.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Blood Pressure; Body Weight; Cardiovascular Physiological Phenomena; Cyclosporine; Dinoprostone; Enzyme Inhibitors; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Nitrates; Nitric Oxide; Nitrites; omega-N-Methylarginine; Reference Values; Renin; Sodium; Thromboxane B2

The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Age Factors; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Body Weight; Female; Flurbiprofen; Humans; Male; Metabolic Clearance Rate; Middle Aged; Prospective Studies; Thromboxane B2

We assessed the effects of low-dose aspirin (0.5 and 15 mg/kg/d) on renal prostaglandin synthesis and action in healthy volunteers using intravenous furosemide as a stimulus. Inhibition of platelet cyclo-oxygenase was assessed by changes in serum thromboxane B2 (TXB2) level. After one week of treatment, ten healthy subjects did not show any change in weight, blood pressure, or diuretic and natriuretic responses to furosemide with either dose of aspirin. Serum TXB2 level was reduced to 3% of control by aspirin 0.5 mg/kg/d and to 0.1% by the higher dose. In contrast, urine excretion of TXB2 was only reduced to 68% and 51% of the placebo value, whereas 6-keto-prostaglandin F1 alpha (6kPGF1 alpha) excretion was not decreased by either dose. Furosemide produced a transient increase in excretion rates of TXB2 and 6kPGF1 alpha that was of lesser duration than the diuretic response. These transient increases were slightly reduced by aspirin. Baseline plasma renin activity was not affected by either dose of aspirin. The brisk increment in plasma renin activity seen ten minutes after furosemide, as well as later values (30 and 240 min) were not changed by aspirin. We conclude that chronic low-dose aspirin can profoundly affect platelet PG production without affecting stimulated renal PGI2 production or plasma renin activity. There is a modest reduction in urine TXB2 excretion that is consistent with a primarily renal source of this metabolite.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aspirin; Blood Platelets; Body Weight; Eicosanoic Acids; Electrolytes; Female; Furosemide; Humans; Male; Radioimmunoassay; Renin; Thromboxane A2; Time Factors

To study the effects of physical exercise on biochemical risk factors for ischaemic heart disease 31 healthy middle aged men undertook regular physical exercise for two months and 29 served as controls in a randomised trial. In the men taking regular exercise serum cholesterol concentrations increased 26% more in the high density lipoprotein subfraction two (HDL2) and decreased 31% more in the subfraction three (HDL3) and 9% more in the low density lipoprotein fraction than in the control group. A tendency towards increased plasma 6-keto-prostaglandin F1 alpha concentration and decreased serum thromboxane B2 concentration was found during the period of regular exercise, but prostaglandin E2 concentrations remained unchanged. The increase in plasma 6-keto-prostaglandin F1 alpha concentration was associated with an increase in serum HDL2 cholesterol concentration in the group taking regular exercise. Our data suggest that mild regular physical exercise favourably influences cholesterol distribution in serum lipoproteins in healthy middle aged men and may have beneficial effects on circulating metabolites of arachidonic acid.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Arachidonic Acids; Body Weight; Cholesterol; Clinical Trials as Topic; Coronary Disease; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, HDL2; Male; Oxygen Consumption; Physical Exertion; Random Allocation; Risk; Time Factors

Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) play an important role in inflammatory bowel diseases (IBDs). We investigated the effects of flavocoxid, a dual COX/LOX inhibitor, in experimental colitis induced with either dinitrobenzenesulfonic acid (DNBS) or dextrane sulphate sodium (DSS) In the first model, colitis was induced in rats by a single intra-colonic instillation (25mg in 0.8ml 50% ethanol) of DNBS; after 24h animals were randomized to receive orally twice a day, flavocoxid (10mg/kg), zileuton (50mg/kg), or celecoxib (5mg/kg). Sham animals received 0.8ml of saline by a single intra-colonic instillation. Rats were killed 4 days after induction and samples were collected for analysis. In the second model, colitis was induced in rats by the administration of 8% DSS dissolved in drinking water; after 24h animals were randomized to the same above reported treatments. Sham animals received standard drinking water. Rats were killed 5 days after induction and samples were collected for analysis. Flavocoxid, zileuton and celecoxib improved weight loss, reduced colonic myeloperoxydase activity, macroscopic and microscopic damage, and TNF-α serum levels. Flavocoxid and celecoxib also reduced malondialdheyde, 6-keto PGF1α and PGE-2 levels while flavocoxid and zileuton decreased LTB-4 levels. In addition, flavocoxid treatment improved histological features and apoptosis as compared to zileuton and celecoxib; moreover only flavocoxid reduced TXB2, thus avoiding an imbalance in eicosanoids production. Our results show that flavocoxid has protective effect in IBDs and may represents a future safe treatment for inflammatory bowel diseases.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Apoptosis; Arachidonate 5-Lipoxygenase; Body Weight; Catechin; CD3 Complex; Celecoxib; Colitis; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Drug Combinations; Eating; Gene Expression Regulation; Hydroxyurea; Leukotriene B4; Lipid Peroxidation; Lipoxygenase Inhibitors; Male; Neutrophil Infiltration; Rats; Rats, Sprague-Dawley; Thromboxane B2; Tumor Necrosis Factor-alpha

Endothelial dysfunction might be involved in the pathogenesis of myxomatous mitral valve disease (MMVD). The aims of this study were (1) to validate an enzyme immunoassay (EIA) for canine 6-keto-prostaglandin (PG)F(1alpha) (prostacyclin metabolite and marker for endothelial function) and (2) to compare plasma and urinary 6-keto-PGF(1alpha) in dogs with asymptomatic MMVD. The study included two breeds predisposed to MMVD and two control groups (Cairn terriers and dogs of different breeds). Echocardiography was used to estimate the severity of MMVD. The intra- and inter-assay coefficients of variation were between 3.1% and 24.5% in the assay range. No echocardiographic parameter was correlated with plasma or urinary 6-keto-PGF(1alpha) (P>0.05), but all control dogs had lower urinary 6-keto-PGF(1alpha) (P<0.02) and the Cairn terriers had higher plasma 6-keto-PGF(1alpha) (P<0.02). The EIA appeared valid for measuring canine 6-keto-PGF(1alpha) in plasma and urine. It is suggested that 6-keto-PGF(1alpha) levels are related to breed and not MMVD in asymptomatic stages.

Topics: 6-Ketoprostaglandin F1 alpha; Age Factors; Animals; Biomarkers; Body Weight; Dog Diseases; Dogs; Echocardiography; Female; Heart Valve Diseases; Immunoenzyme Techniques; Male; Mitral Valve; Mitral Valve Insufficiency; Risk Factors; Severity of Illness Index; Sex Factors

The purpose of this study was to determine whether cyclooxygenase expression in arteries is affected by diabetes. Streptozotocin-injected rats and Goto-Kakizaki rats were used as animal models for type 1 and type 2 diabetes, respectively. Cyclooxygenase-2 expression was induced by lipopolysaccharide. Lipopolysaccharide-induced cyclooxygenase-2 expression was significantly lower in aortas isolated from streptozotocin-injected rats and Goto-Kakizaki rats than in aortas of control rats, while expression level of cyclooxygenase-1 was not affected by lipopolysaccharide and was not different in aortas of the three groups of rats. The level of 6-keto-prostaglandin F(1alpha) that accumulated in the presence of lipopolysaccharide as well as the basal accumulation level in the absence of lipopolysaccharide was significantly lower in aortas of streptozotocin-injected rats and Goto-Kakizaki rats than in aortas of control rats. The net increase in 6-keto-prostaglandin F(1alpha) level in response to stimulation with lipopolysaccharide, which was calculated by subtracting the basal accumulation level from the total accumulation level, was also significantly lower in aortas of streptozotocin-injected rats and Goto-Kakizaki rats than in aortas of control rats. There were no significant differences in the accumulated 6-keto-prostaglandin F(1alpha) levels in the absence or presence of lipopolysaccharide and the levels of basal and lipopolysaccharide-induced cyclooxygenase-2 expression in control or Goto-Kakizaki rat aortas under the conditions of different glucose concentrations in the medium. These results suggest that lipopolysaccharide-induced cyclooxygenase-2 expression and subsequent prostacyclin production are decreased in aortas isolated from both type 1 and type 2 diabetes rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Blood Glucose; Body Weight; Cyclooxygenase 1; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enzyme Induction; Lipopolysaccharides; Male; Membrane Proteins; Rats; Rats, Wistar; Tissue Culture Techniques

We investigated the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in hemodynamic action of leptin. The effect of leptin (1 mg/kg i.p.) on systolic blood pressure (SBP) was examined in lean rats and in rats made obese by feeding highly palatable diet for either 1 or 3 months. Separate groups received NO synthase inhibitor, L-NAME, or EDHF inhibitors, the mixture of apamin+charybdotoxin or sulfaphenazole, before leptin administration. Leptin increased NO production, as evidenced by increase in plasma and urinary NO metabolites and cyclic GMP. This effect was impaired in both obese groups. In lean rats either leptin or EDHF inhibitors had no effect on blood pressure. L-NAME increased blood pressure in lean animals and this effect was prevented by leptin. However, when leptin was administered to animals pretreated with both L-NAME and EDHF inhibitors, blood pressure increased even more than after L-NAME alone. In the 1-month obese group leptin had no effect on SBP, however, pressor effect of leptin was observed in animals pretreated with EDHF inhibitors. In the 3-month obese group leptin alone increased SBP, and EDHF inhibitors did not augment its pressor effect. The results suggest that leptin may stimulate EDHF when NO becomes deficient, e.g. after NOS blockade or in short-term obesity. Although the effect of leptin on NO production is impaired in the 1-month obese group, BP does not increase, probably because EDHF compensates for NO deficiency. In contrast, leptin increases BP in 3-month obesity because its effect on EDHF is also attenuated.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Biological Factors; Blood Pressure; Body Weight; Cyclic GMP; Diet; Indicators and Reagents; Isoprostanes; Leptin; Male; Nitric Oxide; Obesity; Rats; Rats, Wistar

We investigated the hypothesis that thromboxane A2 (TxA2)-prostaglandin H2 receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to ANG II (400 ng x kg(-1) x min(-1) sc for 14 days) using TP-R knockout (TP -/-) and wild-type (+/+) mice. TP -/- had normal basal mean arterial blood pressure (MAP) and glomerular filtration rate but reduced renal blood flow and increased filtration fraction (FF) and renal vascular resistance (RVR) and markers of ROS (thiobarbituric acid-reactive substances and 8-isoprostane PGF2alpha) and nitric oxide (NOx). Infusion of ANG II into TP +/+ increased ROS and thromboxane B2 (TxB2) and increased RVR and FF. ANG II infusion into TP -/- mice reduced ANG I and increased aldosterone but caused a blunted increase in MAP (TP -/- : +6 +/- 2 vs. TP +/+: +15 +/- 3 mmHg) and failed to increase FF, ROS, or TxB2 but increased NOx and paradoxically decreased RVR (-2.1 +/- 1.7 vs. +2.6 +/- 0.8 mmHg x ml(-1) x min(-1) x g(-1)). Blockade of AT1 receptor of TP -/- mice infused with ANG II reduced MAP (-8 mmHg) and aldosterone but did not change the RVR or ROS. In conclusion, during an ANG II slow pressor response, AT1 receptors activate TP-Rs that generate ROS and prostaglandins but inhibit NO. TP-Rs mediate all of the increase in RVR and FF, part of the increase in MAP, but are not implicated in the suppression of ANG I or increase in aldosterone. TP -/- mice have a basal increase in RVR and FF associated with ROS.

Topics: 6-Ketoprostaglandin F1 alpha; Aldosterone; Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Body Weight; Dinoprost; Electrolytes; Epoprostenol; Female; Heart Rate; Hematocrit; Hypertension, Renal; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitrates; Nitrites; Organ Size; Receptor, Angiotensin, Type 1; Receptors, Thromboxane A2, Prostaglandin H2; Renal Circulation; Specific Pathogen-Free Organisms; Thiobarbituric Acid Reactive Substances; Thromboxane B2; Urine; Vascular Resistance; Vasoconstrictor Agents

To investigate the effects of celecoxib on fetal growth, and placental prostanoid and nitric oxide (NO) production in fetal rabbits, pregnant rabbits received celecoxib (30 mg/kg per day) from 13 to 20 days (Cel-A), from 13 to 28 days (Cel-B), or vehicle from 13 to 28 days gestation. Fetal body and organ weights, and measurements of linear growth were recorded. The placentas were weighed and analyzed for prostaglandins (PGs), NO oxidation products (NOx), and total cellular protein levels. Placental prostaglandin E2 (PGE2) and NOx levels increased (P < or = 0.05), while thromboxane B2 levels were suppressed (P < or = 0.01) in Cel-B group. Tail length and brain weight were greater, while lung weights were lower in the Cel-B group (P < or = 0.05). Maternal administration of celecoxib appears to preferentially increase placental vasodilators and decrease placental TxA2, suggesting that the drug may increase uteroplacental perfusion without adverse fetal outcome.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Female; Isoenzymes; Nitric Oxide; Organ Size; Perfusion; Placenta; Pregnancy; Pregnancy, Animal; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pyrazoles; Rabbits; Sulfonamides; Thromboxane B2; Time Factors

To investigate the effect of two types of dietary protein on blood pressure, liver fatty acid desaturation and composition, and urine 6-keto-prostaglandin-F (PGF(1alpha)) level, the metabolite of prostacyclin.. 5-wk-old spontaneously hypertensive rats were fed 20% casein or purified fish protein. The fat source was 5% ISIO oil, which contains 47.9% (omega-6) and 1.7% (omega-3) total polyunsaturated fatty acids. After 2 mo on the diet, systolic blood pressure was reduced with fish protein compared with casein (189.8 +/- 10.5 versus 220.7 +/- 8.7).. Excretion of 6-keto-PGF(1alpha) in urine was negatively correlated with blood pressure. Liver cholesterol and phospholipid concentrations were 1.71- and 1.27-fold lower with fish protein than with casein, respectively. The fish protein diet lowered the 20:4(omega-6) proportion and the ratio of 20:4(omega-6) to 18:2(omega-6) in liver microsomal lipids and phospholipids, which was due to the reduced microsomal Delta6(omega-6) desaturation activity. Dietary protein source did not affect omega-3 fatty acid composition, and this was associated with a similar activation of Delta6(omega-3) desaturation in liver microsomes.. The present data indicated a significant blood pressure-lowering effect caused by fish protein, rather than by casein, that modified the fatty acid composition of liver phospholipids and liver microsomal total lipids.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Caseins; Dietary Fats, Unsaturated; Dietary Proteins; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Fish Proteins; Hypertension; Lipid Metabolism; Lipids; Liver; Male; Microsomes, Liver; Organ Size; Prostaglandins F; Rats; Rats, Inbred SHR

We used rats (the Otsuka Long-Evans Tokushima Fatty strain) as a model of type 2 diabetes to find whether thromboxane (TX) A2 is involved in diabetic nephropathy, and if so, to identify where it is synthesized. We measured urinary excretion of TXB2 and 2,3-dinor-TXB2 in rats up to 60 weeks of age as markers of renal and platelet synthesis of TXA2, respectively. Some diabetic rats were given daily oral doses of OKY-046 (100 mg/kg), a TXA2 synthase inhibitor, starting when they were 10 weeks of age. Healthy Long-Evans Tokushima Otsuka rats served as the controls. Urinary excretion of protein was greater in diabetic rats at 26 weeks than in controls, and the difference increased with age. Urinary excretion of TXB2 by diabetic rats was about 150% that of controls at 14 weeks, and remained at that level. In diabetic rats, urinary excretion of 2,3-dinor-TXB2 increased with age in parallel to increases in proteinuria, but in controls, excretion of these metabolites did not change with age. In diabetic rats, OKY-046 prevented the increase in urinary excretion of both metabolites, and decreased the proteinuria. Histologic examination at 60 weeks showed intraglomerular thrombi in diabetic rats but not in controls. OKY-046 reduced intraglomerular thrombi formation and the score for glomerulosclerosis. When platelet aggregation began, more TXA2 than before was released from the thrombi that formed, and the TXA2 contributed to the progress of nephropathy in this rat model of type 2 diabetes.

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Enzyme Inhibitors; Glomerular Mesangium; Male; Methacrylates; Prostaglandins; Proteinuria; Rats; Rats, Inbred OLETF; Thrombosis; Thromboxane A2; Thromboxane-A Synthase

1 It is known that nonselective cyclo-oxygenase (COX) inhibitors have small but significant effects on blood pressure (BP), most notably in hypertensive patients on antihypertensive medication. Whether selective COX-2 inhibitors also interfere with BP regulation is not well understood. Therefore, we aimed to examine the effect of chronic treatment with a selective COX-2 inhibitor (rofecoxib) on systolic blood pressure (sBP) in normotensive Wistar-Kyoto rats (WKY) and on the developmental changes of sBP in young spontaneously hypertensive rats (SHR). In addition, we investigated a possible influence of salt intake on the effects of COX-2 inhibition on BP in these two rat strains. 2 Rofecoxib dose dependently increased sBP and decreased plasma levels of 6-keto prostaglandin (PG)F(1alpha) in WKY rats fed a normal salt diet (0.6% NaCl, wt wt(-1)), without affecting serum thromboxane (TX)B(2) levels. 3 Rofecoxib significantly elevated sBP in both rat strains fed normal salt or high salt diet (8% NaCl, wt wt(-1)), but not in rats on low salt intake (0.02% NaCl, wt wt(-1)). 4 Rofecoxib significantly decreased plasma levels of 6-keto PGF(1alpha) in both rat strains fed normal or high salt diet, but not in rats during low salt intake. 5 Rofecoxib exerted no influence on the changes of body weight nor on water intake. Plasma renin activity (PRA) and renocortical renin mRNA abundance were not changed by rofecoxib, but plasma aldosterone concentration (PAC) was significantly reduced. 6 These results suggest that chronic inhibition of COX-2 causes an increase of blood pressure that depends on prostacyclin synthesis. Furthermore, this increase is independent on genetic predisposition and can be prevented by salt deprivation. Since water intake and body weight gain were not changed by rofecoxib, fluid retention appears not to be a major reason for the development of hypertension. Similarly, an activation of the renin-angiotensin-aldosterone axis appears to be an unlikely candidate mechanism.

Topics: 6-Ketoprostaglandin F1 alpha; Actins; Aldosterone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drinking; Heart Rate; Hematocrit; Kidney Cortex; Lactones; Male; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; RNA, Messenger; Sodium, Dietary; Sulfones

Chronic infusion of angiotensin-(1-7) [Ang-(1-7)] lowers blood pressure in salt-induced and spontaneously hypertensive (SHR) rats. In the present study, we have examined the acute effect of Ang-(1-7) in salt-induced hypertension using Dahl salt-sensitive rats placed on low (0.3%) or high (8.0% NaCl) salt diets for 2 weeks. Rats fed a high salt diet showed a greater rise in BP than those fed a low salt diet. Ang-(1-7) (24 microg/kg) reduced mean arterial pressure (MAP), enhanced the release of prostacyclin and nitric oxide, and suppressed thromboxane A(2) levels. A-779 (48 microg/kg, i.v), a selective Ang-(1-7) antagonist, partially blocked these effects of Ang-(1-7). The Ang-(1-7)-induced depressor response observed in these animals was related to an increase in vasodilatory prostanoids, a decrease in the constrictor prostanoid thromboxane A(2), and an increase in nitric oxide levels in both plasma and isolated aortic rings.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin I; Angiotensin II; Animals; Blood Pressure; Body Weight; Cyclic GMP; Dinoprostone; Epoprostenol; Hypertension; Male; Nitric Oxide; Peptide Fragments; Platelet Aggregation Inhibitors; Rats; Rats, Inbred Dahl; Rats, Inbred SHR; Salts; Thromboxane A2; Thromboxane B2; Time Factors

It has been reported that estrogens modulate peripheral vascular synthesis of vasodilatory hormones, including prostacyclin. If this occurs in the cerebral circulation, it could have important consequences in the modulation of cerebral hemodynamic function and improvement of stroke outcome. We investigated the hypothesis that in vivo 17beta-estradiol treatment of ovariectomized rats increases cerebrovascular prostacyclin production via elevation of the enzymes responsible for prostacyclin synthesis.. Cerebral blood vessels from 17beta-estradiol-treated and nontreated ovariectomized rats were isolated and examined for prostacyclin synthesis by enzyme-linked immunosorbent assay or for protein levels of cyclooxygenase-1, prostacyclin-synthase, and cytosolic phospholipase A2 by immunoblot analysis.. We report that chronic in vivo 17beta-estradiol treatment significantly enhanced basal prostacyclin synthesis in rat cerebral blood vessels by 2.6-fold over control. 17beta-estradiol treatment also resulted in a 5.1-fold increase of cyclooxygenase-1 protein and a 6.7-fold increase of prostacyclin-synthase protein in the cerebral vasculature. There was no effect of estrogen on levels of cytosolic phospholipase A2.. Our findings suggest that estrogen influences the biosynthesis of prostacyclin, which may be important in the regulation of cerebral blood flow and thrombosis. This finding may shed light on the mechanisms that govern sex-based differences in cerebrovascular disease.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Vessels; Body Weight; Brain; Cell Separation; Cerebrovascular Circulation; Cyclooxygenase 1; Cytochrome P-450 Enzyme System; Epoprostenol; Estradiol; Female; Intramolecular Oxidoreductases; Isoenzymes; Membrane Proteins; Models, Biological; Organ Size; Ovariectomy; Phospholipases A; Phospholipases A2; Prostaglandin-Endoperoxide Synthases; Radioimmunoassay; Rats; Rats, Inbred F344; Thromboxanes; Uterus

Chronic infusion of angiotensin (1-7) [Ang-(1-7)] lowers blood pressure in spontaneously hypertensive rats (SHR). To assess the role of Ang-(1-7) in salt-induced hypertension, Ang-(1-7) (24 microg/kg/hr) or saline was administered chronically via osmotic minipump into the jugular vein of 5-6 wk-old male (M) and female (F) Dahl salt-sensitive rats placed on a high-salt (8% NaCl) diet for 2 weeks. Blood pressure (BP) and heart rate were measured prior to the start of the diet and weekly thereafter. Ang-(1-7) significantly attenuated the BP increase after 1 wk on the diet in both M and F rats, but after 2 weeks only in F rats. Enhanced release of prostacyclin, (6-keto PGF1 alpha), following Ang-(1-7) treatment was observed in both M and F rats. In addition, significant increases in aortic blood flow and plasma levels of nitric oxide were observed in the F rats following Ang-(1-7) treatment. These findings demonstrate that the reduction in BP is due to both prostacyclin and NO and that there is a gender difference in the attenuation of salt-induced hypertension by Ang-(1-7).

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensins; Animals; Aorta; Blood Flow Velocity; Blood Pressure; Body Weight; Dinoprostone; Epoprostenol; Female; Heart Rate; Hypertension; Kidney; Male; Nitric Oxide; Rats; Rats, Inbred Dahl; Salts; Sex Factors; Time Factors

In mice heterozygous for the cyclooxygenase-2 gene (COX-2+/-) the body weight was enhanced by 33% as compared to homozygous COX-2-/- mice. The weights of the gonadal fat pads in COX-2+/- mice were enhanced by 3.5 to 4.7 fold as compared to COX-2-/- mice and by 1.5 to 3.5 fold as compared to wild-type controls+/+ Serum leptin levels and leptin release by cultured adipose tissue of COX-2+/- mice were both elevated as compared to either control or COX-2-/- animals. The basal release of PGE2 or 6 keto PGF1alpha per fat pad over a 24 h incubation of adipose tissue was reduced by 80% and 95% respectively in tissue from COX-2-/- mice. NS-398, a specific COX-2 inhibitor, inhibited leptin release by 27% in adipose tissue from control mice, 31% in tissue from COX-1-/- mice and by 23% in tissue from COX-2+/- mice while having no effect on leptin release by adipose tissue from COX-2-/- mice. These data indicate that heterozygous COX-2 mice develop obesity which is not secondary to a defect in leptin release by adipose tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Adipose Tissue; Animals; Body Weight; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Epididymis; Female; Heterozygote; Humans; Isoenzymes; Leptin; Male; Membrane Proteins; Mice; Mice, Knockout; Nitrobenzenes; Obesity; Organ Size; Prostaglandin-Endoperoxide Synthases; Statistics as Topic; Sulfonamides

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1alpha, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4+/-23.5 vs. 27.0+/-2.6 ng/day; mean +/- SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1alpha by the diabetic rats was high at 14 weeks (52.3+/-12.8 vs. 26.9+/-4.6 ng/day; mean +/- SD, P<.001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Blood Glucose; Body Weight; Creatinine; Diabetes Mellitus, Type 2; Dinoprostone; Disease Models, Animal; Kidney; Male; Prostaglandins; Rats; Rats, Inbred OLETF; Rats, Long-Evans; Thromboxane B2; Thromboxanes

In a previous paper we gave evidence that chronic oral defibrotide antagonizes the noxious effect of developing atherosclerosis in the cardiovascular system. In the present paper we give evidence that defibrotide is still capable of exerting beneficial effects on cardiovascular function once atherosclerosis is established. In fact, there was statistically significant amelioration by defibrotide infusion in the following, all of which were hampered by established atherosclerosis: in rabbit aorta relaxation to acetylcholine, prostaglandin E2, and 6-keto-prostaglandin F1alpha generation from rabbit aortas, rabbit heart left ventricular end-diastolic pressure, coronary perfusion pressure, and left ventricular developed pressure, vasopressor activity of acetylcholine and endothelin-1 on coronary perfusion pressure, and 6-keto-prostaglandin F1alpha generation from the rabbit heart. Since prostacyclin takes part in NO generation, is cellular protective, and inhibits 5-lipoxygenase product synthesis, its increase, caused by defibrotide, could explain defibrotide cardioprotective activity. Prostacyclin activity could be backed by prostaglandin E2, another cardioprotective prostaglandin.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcholine; Animals; Aorta; Arteriosclerosis; Blood Pressure; Body Weight; Cardiovascular Physiological Phenomena; Cholesterol, Dietary; Dinoprostone; Endothelin-1; Fibrinolytic Agents; Heart; In Vitro Techniques; Lipids; Male; Muscle Contraction; Muscle, Smooth, Vascular; Organ Size; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Rabbits; Reperfusion; Ventricular Function, Left

Epidemiologic and animal studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against the incidence of colorectal neoplasia and subsequent mortality. We previously demonstrated that sulindac significantly reduces intestinal tumor load in Apc(Min/+)mice and the tumor regression was not necessarily correlated with prostaglandin biosynthesis. In the present study, we further investigate the relationship of NSAID treatment and tumorigenesis in the Apc(Min/+)mouse model. We demonstrate that indomethacin (9 ppm) is a very potent chemopreventive agent, reducing tumor load by 85% and significantly inhibiting basal and ex vivo prostaglandin formation (P< 0.006 and P< 0.0001, respectively). Aspirin (400 ppm) has a similar impact on reducing prostaglandin levels, but in contrast to indomethacin, is uneffective in reducing the tumor load. The data indicate a discordance between the impact of different NSAIDs on tumorigenesis in Apc(Min/+)mice.

Topics: 6-Ketoprostaglandin F1 alpha; Adenomatous Polyposis Coli; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Arachidonic Acid; Aspirin; Body Weight; Dinoprostone; Eating; Indomethacin; Intestinal Mucosa; Intestinal Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Prostaglandin Antagonists

Sesamin, a nonfat constituent of sesame oil, inhibits Delta(5)-desaturase activity, resulting in accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid (AA) and consequently decreases the formation of proinflammatory 2-series prostaglandins.. We sought to determine whether dietary supplementation with sesamin augments the antiinflammatory effects of dietary linseed oil in rats.. We investigated the effects of continuous tube feedings of emulsions containing safflower oil or linseed oil with sesamin (SO+ and LO+) or without sesamin (SO and LO) on liver fatty acid composition and on endotoxin-induced production of prostaglandin E(2), 6-keto-prostaglandin F(1alpha), and tumor necrosis factor alpha (TNF-alpha) by whole blood from rats (n = 6 per diet group).. We found a significant accumulation of DGLA only in the liver phospholipids of animals fed SO+ and LO+ (1.8 +/- 0.2 and 1.4 +/- 0.3 mol%, respectively), which suggests that sesamin inhibited Delta(5)-desaturation of n-6 fatty acids. These changes were associated with significant reductions in plasma prostaglandin E(2) concentrations in animals fed SO+ compared with those fed SO (P: < 0. 05). Despite a significant reduction in tissue AA content in the LO group, the prostaglandin E(2) concentrations did not differ significantly from those of the SO group. Plasma concentrations of TNF-alpha were significantly lower (P: < 0.05) in the animals fed LO+ than in those fed SO (199 +/- 48 and 488 +/- 121 ng/L, respectively).. These data indicate that in rats, tube feedings of diets containing sesamin exerted antiinflammatory effects that were augmented by concurrent consumption of linseed oil.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Body Weight; Dietary Fats; Dietary Supplements; Dinoprostone; Dioxoles; Emulsions; Fatty Acids; Lignans; Lipopolysaccharides; Liver; Male; Prostaglandins; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.

Topics: 6-Ketoprostaglandin F1 alpha; alpha-Linolenic Acid; Animals; Body Weight; Dietary Fats; Dinoprostone; Docosahexaenoic Acids; Eating; Fatty Acids; Fatty Acids, Omega-3; gamma-Linolenic Acid; Genes, APC; Intestinal Neoplasms; Intestines; Linoleic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Phospholipids

Cyclosporine (CsA) (45 mg/kg/day for 7 days) administration in female Wistar rats induced significant decrease in creatinine clearance (Ccr) and body weight loss (BWL). Urine volume (V) was not altered and proteinuria (PU) not provoked. These changes were associated with increased urinary endothelin 1 (ET-1) and thromboxane B(2)(TXB(2)) concentrations, and decreased urinary ratios of prostaglandin (6ketoPGF(1 alpha)and PGE(2)) to TXB(2)excretions. Nifedipine (NFD) (0.1 mg/kg/day for 7 days), a calcium channel blocker, administrated in addition to CsA, to another group of animals, significantly augmented Ccr and urine V but did not prevent BWL in comparison to CsA-only treated rats. The urinary ET-1 and TXB(2)concentrations displayed significant and non-significant decrease respectively, while the urinary excretion ratios of 6ketoPGF(1 alpha)/TXB(2)and PGE(2)/TXB(2)were significantly enhanced.These observations indicate that the partial protection of NFD in CsA-induced nephrotoxicity could be attributed to augmented urinary prostanoid ratios of renal vasodilators (6ketoPGF(1 alpha)and PGE(2)) to vasoconstrictor (TXB(2)) excretions, and also to reduced release of rather renal origin ET-1, the most potent mamalian vasoconstrictor peptide known to date. In a previous study, we found that NFD only slightly prevented structural renal damage, induced by CsA. So, the NFD protection refers only to functional toxicity and not to structural damage, mediated at least in part by the preservation of relatively high renal TXB(2)levels. However, other nephrotoxic factors and additional mechanisms could also be implicated in this CsA-induced syndrome.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Calcium Channel Blockers; Creatinine; Cyclosporine; Dinoprostone; Dose-Response Relationship, Drug; Endothelin-1; Endothelins; Enzyme Inhibitors; Female; Immunoassay; Kidney; Nifedipine; Proteinuria; Rats; Rats, Wistar; Spectrophotometry; Thromboxane B2; Urine

Patients with human immunodeficiency virus show increased atheroembolism and premature arterial events (stroke, myocardial infarction), but no increased venous thromboembolism. This paper describes an association of elevated lipoprotein(a), a decreased prostaglandin I(2)(PGI(2)) synthesis stimulating plasma factor, diminished PGI(2)-stability in plasma and decreased high-density lipoprotein-cholesterol and apolipoprotein A. It is unclear to what extent these biochemical findings represent an acute phase reaction only or a disturbance in the prostaglandin system. Definitely, they are resulting in severe hemostatic imbalance decreasing local PGI(2)-availability with a dramatic reduction in the cytoprotective capacity favouring the onset of premature arterial events seen in some of the patients.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Apolipoproteins A; Body Weight; Cells, Cultured; Cholesterol, HDL; Endothelium, Vascular; Epoprostenol; Female; HIV Infections; HIV Seropositivity; HIV-1; Humans; Lipoprotein(a); Male; Middle Aged; Radioimmunoassay

1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure of 5/6 nephrectomized spontaneously hypertensive rats with salt loading was examined. 2. All nephrectomized rats were randomly assigned to one of four groups and their diet was changed from a normal- to a high-salt (5.5% NaCl) diet for the next 10 weeks. Either 10 or 50 mg/kg per day cicletanine (low- and high-dose cicletanine, respectively) or 10 mg/kg per day trichlormethiazide were administered to rats during this period once a day. During the experimental period, urine volume, urinary excretion of sodium, protein, prostaglandin (PG) E2 and 6-keto-PGF1 alpha and systolic blood pressure (SBP) were measured every 2 weeks. 3. Systolic blood pressure was significantly reduced by the administration of trichlormethiazide and the higher dose of cicletanine, but not by the lower dose of cicletanine. 4. In contrast with changes to SBP, levels of serum creatinine in rats treated with both doses of cicletanine were significantly lower than in controls (0.57 +/- 0.12, 0.78 +/- 0.12 and 1.68 +/- 0.26 mg/dL for high- and low-dose cicletanine and control, respectively). 5. Urinary excretion of both PGE2 and 6-keto-PGF1 alpha were significantly increased in groups treated with high and low doses of cicletanine compared with control. In rats treated with trichlormethiazide, PGE2 and 6-keto-PGF1 alpha levels were significantly decreased compared with control. 6. In contrast with changes in SBP, marked glomerular sclerosis with hyalinosis found in the control group was not ameliorated by trichlormethiazide treatment. These changes were not observed in rats treated with low- and high-dose cicletanine, particularly those treated with the higher dose of cicletanine. 7. These data suggest that administration of cicletanine has a beneficial protective effect regarding the progression of renal failure, regardless of the level of blood pressure, through a direct and/or indirect action on the glomerulus.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Creatinine; Dinoprostone; Disease Progression; Dose-Response Relationship, Drug; Hypertension, Renal; Male; Nephrectomy; Pyridines; Rats; Rats, Inbred SHR; Renal Insufficiency

The endothelial vasodilation mechanism(s) has been investigated in aortic rings of hypophysectomized male rats as well as hypophysectomized rats treated for 7 days with growth hormone (GH, 400 microg/kg, s.c.) or hexarelin (80 microg/kg, s.c.). Tissue preparations from intact animals were taken as controls. The results obtained indicate that the release of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) from aortic rings of hypophysectomized rats was markedly reduced (51%; p<0.01) as compared with that of control preparations; the peak response to cumulative concentration of endothelin-1 (ET-1, from 10(-11) to 10(-5) M) was increased 2.4-fold (p<0.01) versus controls; the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M) in norepinephrine-precontracted aortic rings was reduced by 39.5+/-4.4%. Pretreatment of hypophysectomized rats with GH or hexarelin markedly antagonized the hyperresponsiveness of the aortic tissue to ET-1 and allowed a consistent recovery of both the relaxant activity of ACh and the generation of 6-keto-PGF1alpha. Collectively these findings support the concept that dysfunction of vascular endothelial cells may be induced by a defective GH function. Because a replacement regimen of GH restored the somatotropic function and increased plasma insulin-like growth factor-I (IGF-I) concentrations in the hypophysectomized rats, it is suggested that IGF-I may have protected the vascular endothelium acting as a biologic mediator of GH action. In contrast to GH, hexarelin replacement neither increased body weight nor affected the plasma concentrations of IGF-I, indicating that its beneficial action on vascular endothelium was divorced from that on somatotropic function and was likely due to activation of specific endothelial receptors.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcholine; Animals; Aorta; Body Weight; Endothelin-1; Endothelium, Vascular; Enzyme Inhibitors; Homeostasis; Human Growth Hormone; Humans; Hypophysectomy; Male; Oligopeptides; omega-N-Methylarginine; Protective Agents; Rats; Rats, Sprague-Dawley; Vasodilation

Severe Mg deficiency changed mineral homeostasis, induced membrane damage, increased lipid peroxidation and cytokine concentrations, and reduced immunocompetence. In order to investigate whether the pathobiochemical effects correlate directly with the degree of Mg deficiency or whether there might be a threshold with no detectable effects above, diets with 70, 110, 208, 330 and 850 ppm Mg were fed to growing Wistar rats. After feeding the diets for 0, 10, 20 and 30 days parameters of free radical action (malondialdehyde and vitamin E content), mineral content (Mg, Ca, Fe) in various tissues (liver, spleen, heart, kidney, muscle) and plasma parameters (Mg, Ca, Fe, alanine- and aspartate-aminotransferase) were measured. After 30 days 6-keto-prostaglandin F1 alpha, thromboxane B2, tumor necrosis factor-alpha, and immunoglobulins (IgG, IgM, IgA) were additionally analyzed. Tissue Mg content was either unchanged or only slightly reduced in severe Mg deficiency. Tissue Fe content rose when the extracellular Mg concentration was below 0.25 mM. There was a close positive correlation between tissue Fe and malondialdehyde content, and malondialdehyde was negatively correlated with vitamin E content. Below a threshold of about 0.25 mM plasma Mg concentration, transaminases increased in plasma. The same threshold could be observed for the increase of tissue Ca content, except in the kidney where calcifications were found already in mild Mg deficiency. Tumor necrosis factor-alpha and 6-keto-prostaglandin F1 alpha were increased when the plasma Mg concentration was below 0.15 mM, and thromboxane B2 was increased when plasma was lower than 0.25 mM. IgG and IgA were significantly reduced below 0.25 mM plasma Mg and IgM below 0.4 mM plasma Mg. Mild Mg deficiency, therefore, can be compensated and might not lead to pathological symptoms if not combined with other pathobiological conditions.

Topics: 6-Ketoprostaglandin F1 alpha; Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Electrolytes; Erythrocytes; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Magnesium Deficiency; Male; Malondialdehyde; Rats; Rats, Wistar; Thromboxane B2; Tumor Necrosis Factor-alpha; Vitamin E

1. Angiotensin II (AngII) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and beta-adrenoceptor stimulation on the production of vascular AngII and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5, 17 and 30 weeks, and age-matched Wistar-Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail-cuff method. Mesenteric arteries were isolated and perfused with Krebs'-Henseleit solution. The outflows of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and AngII were measured by specific radioimmunoassays. 3. The SBP was higher in SHR than in WKY rats in the 17- and 30-week-old groups and increased with age. Basal levels of PGE2 were significantly lower in SHR than in WKY rats. The ratios of 6-keto-PGF1 alpha to TxB2 and PGE2 to TxB2 were significantly lower in 17-week-old SHR compared with age-matched WKY rats. Basal AngII release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of AngII; the magnitude of the increment was greater in WKY rats than in age-matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed. 4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR. Our findings suggest that vascular AngII plays a role in the ageing process and that beta-adrenoceptor-stimulated release of vascular AngII is impaired in SHR.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin II; Animals; Blood Pressure; Blood Vessels; Body Weight; Dinoprostone; Eicosanoids; Hypertension; Male; Mesenteric Arteries; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vascular Resistance

Male rats were treated with growth hormone (GH)-releasing hormone antiserum to induce selective GH deficiency. The chronic administration of hexarelin to these GH-deficient rats had a pronounced protective effect against ischaemic and post-ischaemic ventricular dysfunction. Hexarelin prevented hyper-responsiveness of the coronary vascular bed to angiotensin II and also prevented the reduction in generation of 6-keto-prostaglandin F1alpha in perfused hearts from GH-deficient rats. The most plausible interpretation of these findings is that hexarelin acts via stimulation of specific cardiac and vascular receptors, triggering currently unknown cytoprotective mechanisms that are responsible for resistance to ischaemic insults and for the preservation of the integrity of the endothelial vasodilation function.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin II; Animals; Antibodies; Area Under Curve; Body Weight; Coronary Vessels; Cytoprotection; Endothelium, Vascular; Growth Hormone; Growth Hormone-Releasing Hormone; Heart Ventricles; Male; Myocardial Ischemia; Myocardial Reperfusion; Oligopeptides; Organ Size; Perfusion; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vasodilation

The effects of fasting for 4 days on the isometric developed tension (IDT) and on the metabolism of labelled glucose and arachidonic acid in uteri from intact and spayed (25 days) rats, were explored. Starvation produces a fall in the contractile activity of intact rats, while in ovariectomized ones, no differences can be seen with respect to their controls. Fasting produces a fall in the glucose metabolism of both intact and ovariectomized rats, being more noticeable in the former group. Indomethacin (5 x 10(-6) M) increases the metabolism of labelled glucose in all experimental groups, significantly. The metabolism of exogenous arachidonic acid into different eicosanoids, PGE2, PGF2 alpha, 6-keto-F1 alpha and TXB2, shows that total food deprivation diminishes significantly the production of PGE2 in intact rats. In contrast, in ovariectomized starved rats, PGE2 increases markedly. The rest of the metabolites studied are not influenced by fasting. These results show that the effects of fasting on the contractile activity and on the release of some metabolites from arachidonic acid by the uteri isolated from intact rats are not seen in ovariectomized animals.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Arachidonic Acid; Body Weight; Carbon Dioxide; Dinoprost; Fasting; Female; Glucose; Indomethacin; Isometric Contraction; Ovariectomy; Rats; Thromboxane B2; Uterine Contraction; Uterus

Two groups of rats, ethanol-treated and sucrose-administered control rats, were fed diets with different AA content (0, 2 and 3% weight) for 14 days. Ethanol was administered by gavage at a single daily dose of 3 g/kg body weight. The ethanol-treated rats showed significantly higher levels (p < 0.01) of serum ALT activity. The dietary AA supplement lowered the serum ALT activity and liver triglyceride both in control and ethanol-treated rats. Significantly lower levels of 20:4n - 6 and 20:4n - 6/18:2n - 6 ratio and higher levels of 18:1n - 9 in both the serum and liver triglyceride were observed in the ethanol-treated rats. The AA-supplemented diet induced a marked increase of 20:4n - 6 and subsequent significant decrease of 18:2n - 6 both in the liver and serum phospholipid in control and ethanol-treated rats. 18:1n - 9 in the serum and liver triglyceride in both groups was also markedly decreased by AA supplement. No significant difference was observed in the liver 6-keto-PGF(1 alpha) level between the ethanol-treated and control rats. In the ethanol-treated rats, the level of 6-keto-PGF(1 alpha) was elevated in the rats fed the 3% AA-supplemented diet. Though the liver leukotriene B4 levels were increased by ethanol administration in all rats, these levels were not increased by dietary AA.

Topics: 6-Ketoprostaglandin F1 alpha; Alanine Transaminase; Animals; Arachidonic Acid; Body Weight; Dietary Fats; Ethanol; Fatty Acids; Feeding Behavior; Leukotriene B4; Lipid Metabolism; Lipids; Liver; Male; Organ Size; Rats; Rats, Sprague-Dawley

The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined.. Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated.. The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1.. These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Cholesterol, Dietary; Dietary Fats, Unsaturated; Eating; Fatty Acids, Omega-3; Female; Glucose; Heart; Hyperlipidemias; Kidney; Lipids; Nitroglycerin; Organ Preservation; Rats; Rats, Wistar; Reperfusion; Serotonin; Thromboxane B2; Tromethamine

Plasma 6-keto-prostaglandin F1 alpha and thromboxane B2 levels were determined to evaluate their role as predictive indicators for the development and progression of coronary atherosclerosis in young hypercholesterolemic swine. 32 young swine were randomly assigned to the control or atherogenic diet group for 10, 30, 90, or 180 days. Lipid profiles were obtained at the onset and repeated throughout the study. Radioimmunoassays of plasma 6-keto-prostaglandin F1 alpha and thromboxane B2 were recorded at 10 day intervals in the 10 and 30 day subjects and at 30 day intervals in the 90 and 180 day subjects. Sections from the proximal left anterior descending coronary artery were classified based on their histological evidence of atherosclerosis by light microscopy. Hypercholesterolemia was positively correlated with development of coronary atherosclerosis (r = 0.704). However, plasma 6-keto-prostaglandin F1 alpha, thromboxane B2, and the thromboxane B2:6-keto-prostaglandin F1 alpha ratio were not found to be predictive indicators (p > 0.05) for the development or early progression of coronary atherosclerosis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arteriosclerosis; Body Weight; Diet, Atherogenic; Disease Models, Animal; Epoprostenol; Female; Hematocrit; Hypercholesterolemia; Lipids; Male; Random Allocation; Risk Factors; Swine; Thromboxane A2; Thromboxane B2

Prostaglandin E2 (PGE2) inhibits and prostacyclin (PGI2), stimulates lipolysis in vitro. Their role in initiating nonshivering thermogenesis at birth was investigated in 16 fetal sheep at 129-143 days gestation. In 10 fetuses indomethacin, a prostaglandin synthesis inhibitor, was infused; in 6 fetuses saline was administered as a control. 16 h later birth was simulated in utero. The plasma levels of PGE2 and PGI2 were unaffected by cooling. In the control fetuses, ventilation with oxygen caused PGE2 to fall, PGI2 to rise, and initiated moderate thermogenesis, signaled by a twofold increase in plasma free fatty acids (FFA). After umbilical cord occlusion, PGE2 decreased further (PGI2 was unchanged) and thermogenesis accelerated. In indomethacin-treated fetuses, in which the prostanoids had decreased and remained at approximately 20% normal, cooling initiated moderate nonshivering thermogenesis, and ventilation and cord occlusion caused no further changes. Changes in plasma adenosine were similar in control and indomethacin-treated groups. We conclude that declining PGE2 and rising PGI2 contribute to the initiation of thermogenesis at birth, but that other agents possibly of placental origin may play a contributory role.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine; Animals; Animals, Newborn; Blood Gas Analysis; Body Temperature Regulation; Body Weight; Delivery, Obstetric; Dinoprostone; Epoprostenol; Fatty Acids, Nonesterified; Female; Fetal Blood; Gestational Age; Indomethacin; Oxygen; Oxygen Consumption; Pregnancy; Sheep

Dietary protein restriction ameliorates the decrease in GFR and renal plasma flow that occurs 24 hours after the onset of bilateral ureteral obstruction (BUO). The vasoactive hormones, prostaglandins (PGs) and thromboxane (Tx), have a role in the changes in renal function described above. Thus, we evaluated the effect of dietary protein restriction on the production of PGE2. 6-keto PGF1 alpha and TxB2 and on the activities of cyclooxygenase and phospholipases A2 and C in glomeruli isolated from sham-operated control (SOC) and BUO rats fed a low (6% casein) or a normal protein (23% casein) diet for approximately four weeks. A normal protein diet compared to a low protein diet significantly increased the glomerular production of PGE2, 6-keto PGF1 alpha and TxB2 in SOC rats. Glomeruli of rats with BUO fed a normal protein diet had further increased production of eicosanoids when compared to glomeruli of SOC rats ingesting the same diet. The production rates of eicosanoids correlated well with the activity of cyclooxygenase in the two groups of rats. On the other hand, a low protein diet completely abolished the increase in glomerular eicosanoid production seen in rats with BUO. The synthetic levels of eicosanoids were comparable in low protein-fed SOC and BUO rats, indicating normalization of glomerular eicosanoid production in BUO rats fed a low protein diet. Moreover, there were no significant differences in the activities of cyclooxygenase and phospholipases A2 and C between the SOC and BUO rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Dietary Proteins; Dinoprostone; Eicosanoids; Female; Kidney Glomerulus; Organ Size; Phospholipases; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Thromboxane B2; Ureteral Obstruction

Prostaglandin E2 (PGE2) plays an important role in the maintenance of oral mucosal integrity. In this study, we characterized PGE2 receptor binding in the buccal mucosa of Syrian hamster and assessed the effect of nicotine (NC) and benzo (a) pyrene (BP), the two major ingredients in cigarette smoke, on this receptor. Adult male animals were treated for 4 weeks by apical swabbing of the buccal pouch with corn oil (control, C), 1 mM NC, BP, or NC + BP in corn oil, twice a day, 5 days a week. The results obtained with the untreated group revealed the presence of a specific PGE2 receptor consisting of two binding sites (high affinity with Kd = 1.52 nM and Bmax = 37 fmol/mg protein and low affinity with Kd = 813 nM and Bmax = 1.29 pmol/mg protein). The treatment with NC, BP, and NC + BP caused a significant decrease in PGE2 receptor binding (specific binding: 10.20 +/- 0.42, 6.84 +/- 1.32**, 6.58 +/- 0.67** and 5.88 +/- 1.03** fmol/mg protein; C, NC, BP, and NC+BP, respectively; Mean +/- SD, n = 5, **p < 0.01). The data suggest that decreased receptor binding for PGE2 in the buccal mucosa may be the cause for the adverse effect of cigarette smoke on the health of oral mucosa.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Topical; Animals; Benzo(a)pyrene; Binding, Competitive; Body Weight; Cheek; Cricetinae; Dinoprostone; Epoprostenol; Male; Mesocricetus; Mouth Mucosa; Nicotine; Organ Size; Prostaglandin D2; Receptors, Prostaglandin E

Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post-ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar-Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups (n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B2 (TxB2), 6-keto-PGF1 alpha and PGF2 alpha in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats (n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre-ischemic ibuprofen administration. In the control microdialysis group, levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC. Levels of 6-keto-PGF1 alpha increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB2 and PGF2 alpha levels in both CN and HPC and decreased 6-keto-PGF1 alpha levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals (n = 5), ibuprofen was administered after probe insertion. Only PGF2 alpha levels were measured in this group. Increased levels of PGF2 alpha comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF2 alpha were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibu

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Brain Ischemia; Caudate Nucleus; Cell Death; Dialysis; Dinoprost; Eicosanoids; Hippocampus; Ibuprofen; Neurons; Prosencephalon; Rats; Rats, Inbred WKY; Stereotaxic Techniques

Our purpose was to test the hypothesis that bacterial endotoxin may reduce fetal growth and to assess some of the pathophysiologic mechanisms of such an effect.. Two randomly selected groups of nine guinea pigs at 30 days' gestation were treated with a solution of endotoxin isolated from Bacteroides fragilis or with solvent alone. Antibody titers, glucose, triglycerides, and 6-keto-prostaglandin F1 alpha were determined in maternal or fetal blood samples. Fetal weight was determined at 61 days' gestation.. Endotoxin-treated guinea pigs showed positive antiendotoxin antibody titers, reduced weight gain, and significantly higher serum levels of triglycerides and 6-keto-prostaglandin F1 alpha, but not of glucose, than did sham-treated controls. Fetuses of endotoxin-treated animals had significantly lower birth weights and serum glucose concentrations and significantly higher triglyceride levels than did control fetuses.. Bacteroides fragilis endotoxin causes fetal growth retardation in the pregnant guinea pig, which may be due to alterations in carbohydrate and fat metabolism mediated by cytokine action.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bacteroides fragilis; Blood Glucose; Body Weight; Endotoxins; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Guinea Pigs; Pregnancy; Prospective Studies; Triglycerides

The effects of exercise training on eicosanoid levels were studied in male Wistar rats. One-month-old rats were trained on a drum exerciser at an intensity of around 70% of maximal oxygen consumption for 10 weeks (60 min day-1, 5 days week-1) after familiarization. Some animals of the same age did not exercise and served as a control. Two days after training, several blood vessels, including thoracic aortae, inferior vena cavae, external iliac arteries, external iliac veins, common carotid arteries and jugular veins, were excised and incubated for 10 min. Basal release of prostacyclin from these vessels was determined using [125I]radio-immunoassay (RIA) of 6-keto-PGF1 alpha. The levels of plasma prostacyclin and urinary metabolites of prostacyclin and thromboxane were also determined by RIA. Our results showed that trained animals had lower body weight and urine 11-dehydro-thromboxane B2 levels than the controls (P < 0.001 and P < 0.05, respectively). In contrast, urinary 2,3-dinor-6-keto-PGF1 alpha level was elevated after training (P < 0.05). Nonetheless, prostacyclin levels in plasma and from various dissected vessel segments, except thoracic aorta, did not change significantly after training. These findings suggest that exercise training may affect endogenous eicosanoid levels by increasing the basal release of prostacyclin and reducing the basal thromboxane level.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Cell Count; Body Weight; Epoprostenol; Male; Muscle, Smooth, Vascular; Oxygen Consumption; Physical Exertion; Pulmonary Gas Exchange; Rats; Rats, Wistar; Thromboxane B2; Thromboxanes

1. To investigate possible mechanisms of increased systolic blood pressure after 1 weeks treatment with dexamethasone and its amelioration by fish oil feeding, we have examined the reactivity of aortic rings and perfused mesenteric resistance vessels. 2. Thirty six Sprague-Dawley rats were initially divided into two groups and fed a semisynthetic diet containing either (10% by weight) hydrogenated coconut oil and safflower oil mixture (HCO/S) (24 rats) or fish oil (12 rats) for 5 weeks. From the end of the fourth week, dexamethasone (1.25 mg ml-1) in drinking water, was given to half the rats on hydrogenated coconut oil (HCO/S+Dex) and to the fish oil-fed group (fish oil+Dex). 3. One week of dexamethasone treatment raised systolic blood pressure in the HCO/S+Dex rats but not in the fish oil+Dex group. 4. Endothelium-dependent relaxation to acetylcholine (ACh) was decreased in aortic rings taken from HCO/S+Dex rats compared to rats on HCO/S alone. Relaxant responses to ACh of aortic rings from rats given fish oil+Dex were intermediate between the three groups. Aortic endothelium-independent responses to sodium nitroprusside (SNP) were unchanged between the groups, while aortic contractile responses to noradrenaline were similar in all the groups. 5. In the perfused mesenteric resistance artery, sensitivity to noradrenaline was decreased in rats given fish oil and dexamethasone compared to the other two groups. There were no differences in resistance vessel relaxation to ACh or SNP between groups. 6. Serum corticosterone levels, used as a marker of dexamethasone absorption, were substantially suppressed in dexamethasone-treated rats but levels were higher in rats on fish oil than on HCO/S diets. 7. We suggest that the glucocorticoid-induced rise in systolic blood pressure may be due in part to decreased aortic compliance as a consequence of impaired endothelium-dependent relaxation and perhaps reduced nitric oxide synthesis. Fish oil feeding may ameliorate this rise in blood pressure through (i) changes in dexamethasone absorption, (ii) decrease in reactivity to noradrenaline of perfused mesenteric resistance arteries, (iii) an increase in endothelium-dependent relaxation to ACh or a combination of these three factors.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Corticosterone; Dexamethasone; Electrolytes; Endothelium, Vascular; Fatty Acids; Fish Oils; Glucocorticoids; Hypertension; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Thromboxane B2; Vascular Resistance

The glomerular functional and structural changes in a murine model (MRL-lpr/lpr) of progressive lupus nephritis were studied. Animals were grouped into three age categories. (I, 14 wk; II, 20 wk; and III, 26 wk). GFR fell with age (257 +/- 43, 178 +/- 50, and 150 +/- 40 microL/min for Groups I through III, respectively). Similarly, the ultrafiltration coefficient (Kf) measured on isolated glomeruli fell with time (0.030 +/- 0.006, 0.023 +/- 0.006, and 0.013 +/- 0.002 nL/s/mm Hg, respectively). Both indomethacin and a selective thromboxane receptor antagonist L-670,596 significantly improved GFR in Group II animals to values seen in Group I animals. Neither agent had any effect to increase GFR in older group III animals. L-670,596 had no effect on Kf in Group II or III animals. Glomerular morphometric evaluation demonstrated a progressive rise in glomerular tuft volume, mesangial matrix expansion, proliferation in cells, and a reduction in open capillary loops and epithelial filtration slits with age. However, because of the increase in glomerular volume, calculated surface area remained well preserved over the three respective groups (61 +/- 18, 76 +/- 15, and 71 +/- 13 microns2 x 10(3)). Therefore, the fall in Kf is likely due to a fall in hydraulic permeability (Lp). The ultrastructural component of the glomerular capillary wall that correlated best with Lp was the epithelial filtration slit number per micrometer of glomerular basement length (r = 0.73; P < 0.0001), which suggests that the structural correlate Kf is in the filtration slit length (FSL). Despite the cell proliferation and mesangial matrix expansion in early disease (Group II), the overall FSL remains stable because of a slight increase in filtration surface area and a slight reduction in epithelial slits per micrometer of glomerular basement membrane. The fall in GFR appears to be hemodynamically mediated by thromboxane A2. In older Group III animals, the fall in GFR appears to be due to a 40% reduction in FSL rather than being hemodynamically based. Thus, the early improvement in function with pharmacological agents is deceptive because considerable disease may be present because of adaptive structural changes. Eventually, with disease progression, compensating hemodynamic and structural factors fail to maintain GFR within normal limits.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Carbazoles; Female; Glomerular Filtration Rate; Hematocrit; Indomethacin; Kidney Glomerulus; Lupus Nephritis; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Organ Size; Renal Circulation; Thromboxane B2

The present study was undertaken to examine whether urinary excretions of prostaglandins increase by repeated administration of a non-toxic dose of lithium. Our previous study demonstrated that 2 mEq/kg/day of lithium chloride (LiCl) is not a toxic dose; and therefore, this dose of LiCl in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 7 days into Wistar rats. On day 7, 3% body weight of 1% NaCl solution was given orally; and urine for the determination of PGE2 and 6-keto-PGF1 alpha, a metabolite of PGI2, was collected for 6 hr after dosage. Thereafter, blood samples for measuring plasma renin activity (PRA) were obtained. The urinary amounts of PGE2 and 6-keto-PGF1 alpha in the Li-treated rats were significantly greater than those in the control animals. The values of PRA did not significantly differ between the two groups of rats. These findings indicate that the production of prostaglandins, including those of PGE2 and PGI2, are enhanced during repeated administration of a non-toxic dose of lithium. The enhanced production of prostaglandins might not be mediated through the activated renin-angiotensin system.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Chlorides; Dinoprostone; Drug Administration Schedule; Injections, Intraperitoneal; Lithium; Lithium Chloride; Male; Rats; Rats, Inbred Strains; Renin; Sodium

Studies, performed in rabbits, examined the effect of feeding a high cholesterol diet and/or a calcium antagonist, nifedipine, on renal microvascular prostacyclin biosynthesis and cholesterol accumulation. After 30 days, cholesterol-fed rabbits had elevated serum and tissue cholesterol levels associated with decreased microvascular prostacyclin biosynthesis and histologic evidence of microvascular and glomerular lipid accumulation. Nifedipine reduced tissue cholesterol levels, enhanced prostacyclin biosynthesis, and reduced the histologic evidence for lipid accumulation in renal microvessels and glomeruli. These studies suggest that calcium antagonists may have a beneficial effect in preventing the tissue cholesterol accumulation associated with a high-cholesterol diet and further suggest that these agents may have beneficial effects in the treatment of renal diseases associated with microvascular or glomerular lipid accumulation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Cholesterol; Cholesterol Esters; Cholesterol, Dietary; Kidney; Microcirculation; Nifedipine; Rabbits

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Epoprostenol; Female; Fetus; Humans; Pre-Eclampsia; Pregnancy; Radioimmunoassay; Renin; Thromboxane A2

The effect of two structurally unrelated aldose reductase inhibitors, sorbinil and ponalrestat, on glomerular prostaglandin production and urinary albumin excretion was investigated in rats with diabetes induced by streptozotocin. It was found that both aldose reductase inhibitors, when administered from the time of induction of the diabetes, significantly decreased the raised urinary albumin excretion in the diabetic rats, although it remained elevated compared with non-diabetic rats. Glomerular prostaglandin E and 6-keto-prostaglandin F1 alpha production was significantly increased in glomeruli obtained from the diabetic rats. Inhibition of aldose reductase caused a reduction in the raised glomerular prostaglandin production, although this remained above that observed in the non-diabetic rats. Subsequent experiments were performed to determine whether the effects of the aldose reductase inhibitors could be explained by effects on glomerular filtration rate. It was found that ponalrestat, at a dose which markedly reduced urinary albumin excretion, did not significantly affect glomerular filtration rate in non-diabetic rats, rats with untreated streptozotocin-induced diabetes and rats with diabetes partially treated with low dose insulin. Glomerular sorbitol concentrations were significantly elevated in untreated diabetic rats as early as two weeks after the induction of diabetes. It is concluded that the administration of aldose reductase inhibitors from the time of induction of diabetes significantly reduces glomerular prostaglandin production and urinary albumin excretion. The latter effect is not due to an effect on glomerular filtration rate. Increased polyol pathway activity may account in part for the increased glomerular prostaglandin production and urinary albumin excretion in early experimental diabetes.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Aldehyde Reductase; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Glomerular Filtration Rate; Hypoglycemic Agents; Imidazoles; Imidazolidines; Kidney Glomerulus; Male; Phthalazines; Prostaglandins E; Rats; Rats, Inbred Strains; Reference Values

To examine the effects of endogenous thromboxane A2 on the development of diabetic nephropathy, we administered OKY-046, an inhibitor of thromboxane synthesis, to streptozotocin-induced diabetic rats. Animals were divided into three groups; nondiabetic control, diabetic, and diabetic with OKY-046, and were sacrificed 16 weeks after experimental procedures. The chronic oral administration of OKY-046 to diabetic rats significantly decreased plasma and urinary thromboxane B2 levels. Urinary protein excretion and serum glucose levels were significantly lower in the OKY-046-treated diabetic rats than in the untreated diabetics (60.8 +/- 23.2 vs. 94.1 +/- 33.4 mg/day in the 16th week, p less than 0.05 and 424.4 +/- 93.3 vs. 614.4 +/- 102.3 mg/dl in the 16th week, p less than 0.01, respectively). Platelet aggregation was inhibited by OKY-046. Blood urea nitrogen was unaffected. Ultrastructural examination revealed that the thickness of glomerular basement membrane was markedly thinner in the OKY-046-treated diabetic rats than in the untreated diabetics (197.4 +/- 29.6 vs. 288.6 +/- 46.9 nm, p less than 0.01). These results suggest that thromboxane A2 may play an important role in the development and progression of diabetic nephropathy in rats.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Blood Glucose; Blood Pressure; Blood Urea Nitrogen; Body Weight; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Insulin; Kidney; Male; Methacrylates; Microscopy, Electron; Platelet Aggregation; Proteinuria; Rats; Rats, Inbred Strains; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

We tested the hypothesis that lipopolysaccharide (LPS)-induced myocardial dysfunction is mediated by cyclooxygenase-derived metabolites of arachidonic acid or platelet activating factor (PAF). Ether-anesthetized rats were injected iv with normal saline (NS; 2.5 ml/kg), ibuprofen (cyclooxygenase inhibitor; 15 mg/kg), or SDZ 64-688 (PAF receptor antagonist; 5 mg/kg). Thirty minutes later, the rats were injected iv with NS (5 ml/kg) or Escherichia coli 0111:B4 LPS (20 mg/kg). Two hours later, atria were harvested, connected to an isometric force transducer-amplifier-recorder apparatus, and maintained in vitro in oxygenated 37.5 degrees C Krebs--Henseleit buffer. Force of contraction indexed to body weight (FOCI; g/kg) was significantly (P less than 0.05) lower in the NS/LPS group (N = 7) than in the NS/NS group (N = 7). Pretreatment with ibuprofen (ibuprofen/LPS group; N = 8) did not affect the adverse effect of LPS on atrial FOCI. In contrast, pretreatment with SDZ 64-688 (64-688/LPS group; N = 8) ameliorated (P less than 0.05) the deleterious effect of LPS on contractility. The PAF antagonist did not manifest intrinsic positive inotropic activity (64-688/NS group; N = 8). These results support the notion that LPS-induced myocardial dysfunction in the rat is mediated, at least in part, by PAF.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Depression, Chemical; Endotoxins; Escherichia coli; Heart Rate; Ibuprofen; In Vitro Techniques; Lipopolysaccharides; Male; Myocardial Contraction; Platelet Activating Factor; Rats; Rats, Inbred Strains

The effects of low dose indomethacin therapy in primary prevention of diet-induced atherosclerosis of rhesus monkeys was studied. The parameters studied were serum cholesterol concentration, thromboxane A2 (T x B2), prostacyclin (6-keto-PGF1 alpha) in serum/plasma, and the extent and intensity of coronary atherosclerosis. Although indomethacin did not affect serum cholesterol, it reduced serum T x B2 significantly (P less than 0.01). Plasma 6-keto-PGF1 alpha was not restored to the pretreatment level. A significant protective role of the drug was noted as far as coronary atherosclerosis is concerned (P less than 0.01).

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Cholesterol; Coronary Artery Disease; Diet, Atherogenic; Disease Models, Animal; Indomethacin; Macaca mulatta; Male; Thromboxane A2

Previous studies have suggested a link between hyperfiltration and enhanced polyol pathway activity in the streptozotocin diabetic rat. In the present study we examined the relationship between glomerular sorbitol content, a measure of polyol pathway activity and glomerular filtration rate (GFR), as a function of plasma glucose and time after induction of diabetes. GFR is increased by 1 to 2 weeks in the untreated streptozotocin diabetic rat but falls to values equal to or below control by 2 months. Treatment of diabetic rats with a low dose of insulin to achieve moderate hyperglycemia results in the maintenance of elevated GFR for 2 months. Glomerular sorbitol content in the 1- to 2-week diabetic rats was not significantly different from values in glomeruli from control rats at 1 to 2 weeks but was 11-fold higher than control by 2 months in the untreated diabetic rat. Treatment of diabetic rats with insulin to achieve moderate hyperglycemia resulted in values for glomerular sorbitol content that were not different from control. Thus, elevated GFR was not associated with elevated glomerular sorbitol content in the 1- to 2-week diabetic rat and was dissociated from elevated glomerular sorbitol content in the 2-month diabetic rat. Treatment of 1- to 2-week diabetic rats with sorbinil prevented the rise in GFR observed at this time despite the fact that sorbitol content of glomeruli was not elevated. These results suggested that sorbinil was reducing GFR in the diabetic rat by a mechanism other than aldose-reductase inhibition. The synthesis of vasodilatory prostaglandins by isolated glomeruli and the activity of phospholipase A2 in the particulate cell fraction of glomerular homogenates is higher in 1- to 2-week diabetic rats compared with controls, a finding that may contribute to the elevated GFR in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Aldehyde Reductase; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dinoprostone; Female; Fructose; Glomerular Filtration Rate; Imidazoles; Imidazolidines; Kidney; Kidney Glomerulus; Organ Size; Phospholipases A; Phospholipases A2; Rats; Rats, Inbred Strains; Reference Values; Sorbitol; Sugar Alcohol Dehydrogenases

The vasodepressor responses to intravenous injections of arachidonic acid, and the formation of its metabolites, were studied in rats made diabetic 1 or 2 weeks after a 1-dose alloxan treatment. Arachidonic acid dose-dependently decreased the diastolic blood pressure in normal animals, but this hypotensive effect was significantly weaker in 2-week postalloxan-treated rats. Indometacin abolished arachidonic-acid-induced depressor responses in both normal and diabetic animals. Hypotension induced by sodium nitroprusside was of the same magnitude in non-diabetic and insulin deficient rats. Plasma levels of thromboxane B2 were significantly increased in both the 1- and 2-week diabetic rats, being greater in the latter group; those of 6-keto-PGF1 alpha remained unchanged during the 2-week diabetic period. It is concluded that the attenuation by diabetes of depressor responses to arachidonic acid could be due to changes in the thromboxane/prostacyclin balance, with thromboxane formation being elevated whereas prostacyclin generation remains unaffected.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Male; Nitroprusside; Rats; Rats, Inbred Strains; Thromboxane A2; Thromboxane B2

We examined the relationship between glomerular filtration rate (GFR), as assessed by inulin clearance, and glomerular prostaglandin and thromboxane production as a function of glycemic control in control rats and rats that had had streptozocin-induced diabetes for 2 months. In severely hyperglycemic (plasma glucose level 644 +/- 40 mg/dl) rats with streptozocin-induced diabetes that had not been treated with insulin, GFR was reduced to values below those in control rats by 2 months, whether data were expressed as milliliters per minute or as a function of kidney weight. By contrast, treatment of the diabetic rats with insulin to maintain moderate hyperglycemia (plasma glucose concentration 398 +/- 40 mg/dl) resulted in a persistent elevation of GFR compared with values in control rats. Basal production of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolic product of prostaglandin I2 (PGl2), by glomeruli isolated from the moderately hyperglycemic rats was higher than corresponding values of glomeruli from control rats. Differences in PGE2 and 6-keto-PGF1 alpha production by glomeruli from moderately hyperglycemic and control rats were abolished by addition of arachidonate to the incubation mixture, supporting a role for enhanced availability of arachidonate in the mediation of altered vasodilatory prostaglandin production. By contrast, glomerular production of thromboxane B2 (TXB2), the stable metabolic product of thromboxane A2 (TXA2), was not different in moderately hyperglycemic rats compared with controls. Thus, enhanced production of vasodilatory prostaglandins by glomeruli from moderately hyperglycemic rats was associated with an increase in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dinoprostone; Female; Glomerular Filtration Rate; Insulin; Kidney Glomerulus; Organ Size; Prostaglandins; Rats; Rats, Inbred Strains; Streptozocin; Thromboxane B2; Thromboxanes

Possible etiological factors of cyclosporine (CyA) induced hypertension were investigated in 10 bone marrow transplanted (BMT) patients followed during one week before and 3 weeks after transplantation. Diastolic blood pressure increased significantly after CyA in 4 patients (75 +/- 1 to 94 +/- 2 mmHg) but remained unchanged in 6 others (83 +/- 1 to 87 +/- 1 mmHg). Plasma renin activity on CyA was significantly lower in the hypertensive (0.6 +/- 0.1 ng/ml/hour) than in the normotensive group (1.1 +/- 0.2 ng/ml/hour). Serum creatinine rose significantly during CyA in hypertensive (0.70 +/- 0.04 to 0.99 +/- 0.07 mg/dl) but not in normotensive patients (0.74 +/- 0.06 to 0.81 +/- 0.03 mg/dl). The rise in serum creatinine was correlated with the increase of blood pressure. Neither body weight nor 6 keto PGF1 alpha plasma level changed during CyA. CyA dosage and plasma level were similar in hypertensive and normotensive patients. These data confirm the high incidence of CyA induced hypertension in BMT patients. In addition, they demonstrate that hypertension is not related to the renin-angiotensin axis but well to renal impairment.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Body Weight; Bone Marrow Transplantation; Creatinine; Cyclosporins; Female; Humans; Hypertension; Male; Middle Aged; Renin

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Creatinine; Cyclosporins; Dinoprostone; Kidney; Prostaglandins E; Pyridines; Rats; Thromboxane B2; Thromboxane-A Synthase

1. Dietary suppression of prostanoid synthesis with fish oils has had little effect on blood pressure in models of experimental hypertension in rats. However, a pressor effect of dietary fish oils was observed in spontaneously hypertensive rats (SHR) subject to 1 week of salt loading. 2. Animals were allocated to semisynthetic diets containing either 10% by weight Max EPA fish oil or a control diet of coconut oil, and studied after receiving 1.5% saline for 4 weeks. 3. Within the first week of salt loading, SHR-fed fish oil showed an increase in blood pressure (mean = 9 mmHg) relative to controls. This effect was transient, and after the first week of salt loading there was little difference in blood pressure between the two dietary groups. 4. Following dietary treatment there were substantial changes in plasma fatty acid composition with a 48% decrease in arachidonic acid content of fish oil-fed rats compared with control animals. Rats on the fish oil diet showed a threefold decrease in serum thromboxane generation. Prostacyclin production by incubated segments of aorta was reduced by more than 50% compared with the coconut oil-fed control group. 5. SHR on the fish oil diet showed increased urine volume and sodium excretion, presumably due to increased fluid and salt intake. 6. This study shows that dietary suppression of prostacyclin synthesis is associated with only a minor effect on blood pressure in long-term salt loading of SHR.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Body Weight; Chromatography, Gas; Diet; Eicosanoids; Fatty Acids, Nonesterified; Fish Oils; Hypertension; Male; Platelet Activating Factor; Potassium; Rats; Rats, Inbred SHR; Sodium; Thromboxane B2; Urodynamics

Previous studies from our laboratory have demonstrated transient effects on renal function by etodolac, 200 mg b.i.d. The current study assessed the effects of a larger dose of etodolac (500 mg b.i.d.) to explore the time course of its renal effects and to determine whether the transient effect would become more prolonged with a larger dose. We studied 10 normal subjects and nine patients with renal insufficiency, examining the effects of the first 500 mg dose of etodolac as well as 4 days of b.i.d. administration. In both groups, etodolac transiently decreased fractional excretions of sodium and chloride and urinary prostaglandin E2. In patients, etodolac also transiently decreased inulin and para-aminohippuric acid clearances and urinary 6-keto-prostaglandin F1 alpha. Chronic administration caused no changes in renal function in either group. In summary, in this relatively small group of patients, high-dose etodolac caused only transient, fully reversible effects on renal function, the cumulative effect of which was negligible.

Topics: 6-Ketoprostaglandin F1 alpha; Acetates; Adult; Aged; Aldosterone; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Dinoprostone; Etodolac; Humans; Kidney; Middle Aged; Potassium; Prostaglandins E; Reference Values; Renin; Sodium

Monocrotaline pyrrole (MCTP) causes pulmonary endothelial cell injury and pulmonary hypertension in rats. Damage to endothelial cells in culture has been associated with altered prostacyclin (PGI2) production; therefore, it was of interest to determine if MCTP affected pulmonary PGI2 production. Release of the stable metabolites of PGI2 and thromboxane A2, 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TxB2), respectively, was examined in isolated, buffer-perfused lungs from MCTP-treated rats at times when elevated pulmonary arterial pressure is first observed (day 7) and when the pulmonary hypertensive state has existed for some time (day 14), 6-keto PGF1 alpha release was not affected by MCTP treatment 7 or 14 days after a single intravenous injection of MCTP. TxB2 release was also unaffected at day 7, however 14 days after treatment TxB2 release was greater in lungs from MCTP-treated rats compared to controls. The concentration of both 6-keto PGF1 alpha and TxB2 increased when arachidonic acid was infused into lungs from control or treated rats. These data indicate that MCTP treatment increases the release of TxB2 from isolated lungs at a time when pulmonary hypertension is well-established, but not during early development of pulmonary hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Body Weight; Hydrostatic Pressure; Hypertension, Pulmonary; Lung; Male; Monocrotaline; Organ Size; Perfusion; Pyrrolizidine Alkaloids; Rats; Thromboxane B2; Time Factors

Selenium is an essential component of glutathione peroxidase, which reduces free and esterified hydroperoxides of polyunsaturated fatty acids. Adequate glutathione peroxidase activity could be important for the maintenance of prostacyclin synthesis by blood vessels, since hydroperoxides can inhibit the formation of this substance. We have investigated the effects of dietary selenium deficiency on glutathione peroxidase activity and the synthesis of 6-oxoprostaglandin F1 alpha and monohydroxy and trihydroxy metabolites of polyunsaturated fatty acids by aorta. The latter products can be formed either by the actions of cyclooxygenase or lipoxygenase or by lipid peroxidation. Aortic glutathione peroxidase activity was reduced by over 80% by feeding rats a selenium-deficient diet for 4 weeks, and to undetectable levels after 6 weeks. There were no appreciable differences in the levels of free and esterified oxygenated metabolites of linoleic acid or arachidonic acid between the control and treated groups after 4 weeks. However, after 6 weeks, there were modest, but statistically significant reductions in the formation of 6-oxoprostaglandin F1 alpha and monohydroxy products formed by cyclooxygenase. On the other hand, the amounts of esterified 18:2 metabolites appeared to be higher in aortae from animals on the selenium-deficient diet, although only the increase in esterified 9-hydroxy-10,12-octadecadienoic acid was statistically significant. These results suggest that selenium deficiency can affect the formation of prostacyclin and other oxygenated metabolites of polyunsaturated fatty acids by aorta, possibly by increasing lipid peroxidation. However, the differences between control and selenium-deficient rats after 6 weeks were not very dramatic, in spite of the fact that glutathione peroxidase activity was undetectable. It would therefore appear that additional mechanisms are also involved in controlling the levels of lipid hydroperoxides in aorta.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acid; Arachidonic Acids; Body Weight; Dinoprostone; Esterification; Fatty Acids, Unsaturated; Glutathione Peroxidase; Linoleic Acid; Linoleic Acids; Lipid Peroxides; Lipoxygenase; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Rabbits; Rats; Rats, Inbred Strains; Selenium

1. This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in DOCA/salt-treated rats. 2. After an initial 4 week period on either a 2-series PG 'inhibitory' diet of fish oil (Max EPA), A 'stimulatory' diet of safflower oil or a control diet of saturated fat, three groups of rats were placed on a DOCA/salt regimen for a further 4 weeks. Another group on the saturated fat diet continued their diet without DOCA/salt administration. 3. All the DOCA-treated groups showed a marked increase in blood pressure. However, both polyunsaturated fat (PUFA)-fed groups had blood pressures significantly lower then the saturated fat control. 4. Rats on the Max EPA showed impaired ability to generate prostanoids in vitro (serum, aorta and kidney) and in vivo (urinary PG excretion). DOCA administration increased urinary PGE2 excretion. 5. Thus, dietary suppression of 2-series PG is not accompanied by accelerated DOCA/salt hypertension. The reduction in blood pressure observed in both the safflower and Max EPA-fed groups may be due to PUFA-induced changes in cell membrane fluidity.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Body Weight; Desoxycorticosterone; Dietary Fats; Electrolytes; Hypertension; Kidney; Lipids; Male; Prostaglandins; Rats; Rats, Inbred Strains; Renin; Sodium Chloride; Thromboxane B2

Reduction of renal mass in the rat results in an increased glomerular prostaglandin (PG) and thromboxane (TX) formation that modulates renal hemodynamics. To evaluate whether dietary protein intake could exert effects on renal PG and TX formation after reduction of approximately 70% of renal mass, rats with remnant kidneys were placed on either a high-protein (HP) or a low-protein (LP) diet. After 2 wk on the diet, proteinuria, glomerular filtration rate (GFR), urinary PGE2 excretion, and glomerular PGE2, 6-keto PGF1 alpha, and TxB2 biosynthesis were significantly greater in the rats on HP diets. Two-wk administration of the thromboxane synthesis inhibitor UK 38485 reduced renal TxB2 formation by approximately 70%. In addition, chronic UK 38485 treatment significantly inhibited papillary PGE2 production. Neither chronic nor bolus administration of UK 38485 had an effect on proteinuria or GFR in rats on HP diets. Chronic UK 38485 treatment, however, reduced GFR and proteinuria in rats on LP diets. The bolus administration of UK 38485 did not alter GFR in animals receiving a LP diet. The cyclooxygenase inhibitor indomethacin reduced GFR only in rats on HP diets. The data demonstrate that HP intake stimulates renal prostanoid formation. The increased prostaglandin formation on HP intake modulates GFR in these rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Body Weight; Dietary Proteins; Dinoprostone; Imidazoles; Indomethacin; Inulin; Kidney Glomerulus; Organ Size; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Thromboxane B2

Renal prostaglandins may be important in the modulation of compensatory renal growth. Reductions in renal mass are associated with increased synthesis of these substances by the remaining kidney, and inhibition of prostaglandin synthesis diminishes renal function in partially nephrectomized animals and in patients with reduced functioning renal mass. We examined the effects of uninephrectomy and treatment with indomethacin on renal prostaglandin E2 and 6-keto prostaglandin F1 alpha concentrations in adult male Sprague Dawley rats. The renal content of these prostaglandins was significantly increased in the remaining kidney two days following uninephrectomy (p less than 0.01). Treatment with 5 mg/kg/day of indomethacin over this period abolished the compensatory increase in renal prostaglandin synthesis and significantly attenuated compensatory increases in renal mass, protein and RNA concentrations (p less than 0.05). No alterations in kidney weight, protein or RNA concentrations were found in intact animals treated with the same dose of indomethacin. These findings suggest renal prostaglandins may participate in the biological events leading to compensatory renal growth.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Dinoprostone; Indomethacin; Kidney; Male; Nephrectomy; Organ Size; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains

The effects were determined of dietary fat and selenium (Se) levels on prostaglandin (PG) production in rat blood, kidney, and colon mucosa. For 30 weeks, male Wistar-derived MRC rats were prefed diets containing low (6 g/367 kcal) or high (20 g/367 kcal) levels of fat with one of three Se supplements from sodium selenite: 0.0, 0.1, or 2.0 ppm Se. PG production was stopped by adding aspirin immediately following removal of the blood, kidney, and colon samples. Separate samples were allowed to incubate 10 or 60 minutes before blockage of PG production for determination of ex vivo PG production. Prostaglandin E2 (PGE2), thromboxane B2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay following separation on silicic acid columns. Basal levels of the three PGs were not influenced by diet. PGE2 production in the colon was highest in the group fed the high-fat diet that contained 2.0 ppm Se at 10 and 60 minutes, but PGE2 production in the blood and kidney were not altered by diet. Thromboxane B2 production in the rats' blood was higher in those prefed high-fat diets, but it was not influenced by dietary Se. Production of 6-keto-PGF1 alpha in the blood and thromboxane B2 and 6-keto-PGF1 alpha production by the kidney and colonic mucosa were not influenced by either dietary fat or Se.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Colon; Dietary Fats; Dinoprostone; Kidney; Male; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Selenium; Time Factors

The effect of spironolactone on the urinary excretion of prostaglandins was studied in patients with liver cirrhosis and ascites. Patients were kept in bed and given a sodium-restricted diet for at least 4 days before spironolactone treatment was considered. Starting from the 5th day of protocol, patients were treated with this diuretic if their spontaneous weight loss had been less than 600 g during the 2 previous days. Patients were distributed in groups according to weight loss during the first 4 days on diuretic therapy: Group I (high responders), II (medium responders) and III (low responders). Group I patients showed higher basal values (4th day of protocol) of urinary sodium (P less than 0.02) and urinary 6-keto-PGF1 alpha (P less than 0.02) than the other patients, but there were no significant differences in the basal excretion rates of PGE2 nor TXB2 among the groups. The therapeutic requirement for spironolactone treatment in patients from Group I was delayed as compared with the other two groups (P less than 0.001) due to the fact that their spontaneous weight loss took place over a long period. For all patients, spironolactone administration produced a significant increase in 6-keto-PGF1 alpha excretion (P less than 0.01) without affecting significantly urinary elimination of PGE2 nor TXB2. A close relationship was found between the spironolactone-induced increments in urinary sodium and urinary 6-keto-PGF1 alpha excretion (r = 0.74, P less than 0.001). It is suggested that the ability of the kidney to synthetize prostacyclin can influence the natriuretic response to spironolactone therapy in patients with liver cirrhosis.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Ascites; Body Weight; Dinoprostone; Female; Humans; Kidney; Liver Cirrhosis; Male; Middle Aged; Prostaglandins; Prostaglandins E; Sodium; Spironolactone; Thromboxane A2

The effect of streptozotocin-induced diabetes during pregnancy in rats on prostacyclin synthesis in aorta and heart of offsprings was investigated. Although the aortic and heart syntheses of 6-keto-PGF1 alpha in the offsprings of diabetic rats were not altered at birth, a significant rise in aorta and a decrease in the heart were evident at weaning. At weaning, offsprings of diabetic rats also show a significant rise in plasma cholesterol. These studies show that maternal diabetes might cause effects in the offspring which might become evident in later life.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Suckling; Aorta; Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Experimental; Female; Maternal-Fetal Exchange; Myocardium; Pregnancy; Pregnancy in Diabetics; Rats; Triglycerides

A semisynthetic diet containing adequate amounts of vitamin E and 10% (w/w) of a mixture of polyunsaturated oils subjected to heating and characterized by elevated indexes of thermal alteration (polar component, dimer triglyceride, altered triglyceride contents and reduced alpha-tocopherol levels) was fed to growing male rats for a period of eight weeks. It resulted in a selective alteration of the production of vascular eicosanoids (elevation of platelet thromboxane formation and decrease of vascular prostacyclin release) compared to the values found in rats fed a diet containing a fresh mixture of polyunsaturated oils. Major nutritional parameters, plasma lipids and the fatty acid profiles of plasma, liver and heart lipids were not different in the two groups of animals. Supplementation of an excess vitamin E (300 mg/kg) to the diet containing heated fat neutralized the adverse effects of heated fat on vascular eicosanoid production.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Blood Platelets; Body Weight; Cooking; Diet; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Hot Temperature; In Vitro Techniques; Lipids; Male; Nutritional Physiological Phenomena; Organ Size; Platelet Aggregation; Rats; Thromboxane B2; Thromboxanes; Time Factors; Vitamin E

The contribution of sex steroids to sex-related differences in renal prostaglandin dehydrogenase activity and urinary prostaglandin excretion was examined in 7-8-week-old male and female rats subjected to sham-operation or gonadectomy at 3 weeks of age. Rats were injected subcutaneously twice over a 6-day interval with vehicle (peanut oil, 0.5 mg/kg) or with depot forms of testosterone (10 mg/kg), estradiol (0.1 mg/kg), progesterone (5 mg/kg), or with estradiol and progesterone combined (0.1 and 5 mg/kg). After the second injection, 24-h urine samples were collected for prostaglandin measurement by radioimmunoassay; the rats were killed, and renal and pulmonary prostaglandin dehydrogenase activities were determined by radiochemical assay. Renal prostaglandin dehydrogenase activity was 10-times higher in intact male rats than in intact females. Gonadectomy increased renal prostaglandin dehydrogenase activity 4-fold in females, but had no effect in males; estradiol, alone or combined with progesterone, markedly suppressed renal prostaglandin dehydrogenase activity in both sexes, while testosterone or progesterone alone had no effect. Pulmonary prostaglandin dehydrogenase did not differ between the sexes and was unaffected by gonadectomy or sex-steroid treatment. Intact female sham-operated rats excreted 70-100% more prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in urine than did males; gonadectomy abolished the difference in urinary prostaglandin E2 excretion. Estradiol decreased urinary prostaglandin E2 in females but not in males; treatment with other sex steroids did not alter urinary prostaglandin excretion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Dinoprost; Dinoprostone; Estradiol; Female; Hydroxyprostaglandin Dehydrogenases; Kidney; Lung; Progesterone; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Sex Factors; Testosterone

This study was designed to investigate relationships between dietary potassium and the renal prostaglandin system in rats. The potassium content of the diet was 0.162 mmol/g during the control period and 0.004, 0.162, 1.351, or 2.702 mmol/g during the experimental period. Relative to control data in rats fed a 0.162 mmol/g potassium diet, the urinary excretion of 6-keto-PGF1 alpha was not affected by high potassium intake but increased (P less than 0.05) by 25% in rats fed a low potassium diet for 13 days and was associated with reduction of plasma potassium and with elevation of both plasma renin and net release of 6-keto-PGF1 alpha from renal inner medulla slices incubated in Krebs solution. The excretion of PGF2 alpha was not affected by low potassium intake but increased (P less than 0.05) by about twofold in rats fed a potassium-rich diet (1.351 and 2.702 mmol/g) for 13 days and was associated with elevation of plasma potassium concentration, renal prostaglandin 9-keto-reductase activity, and urinary excretion of kallikrein and vasopressin. The urinary excretion of PGE2 was not altered in rats fed either low or high potassium diets. Altogether, these results indicate selective influence of dietary potassium on the urinary excretion of prostaglandins in the rat.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Diet; Dinoprost; Dinoprostone; Hydroxyprostaglandin Dehydrogenases; Kallikreins; Kidney; Male; Potassium; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Renin; Vasopressins; Water-Electrolyte Balance

This study was designed to examine the effect of dexamethasone treatment on tissue and urinary prostanoids, and to determine whether inhibition of prostaglandin biosynthesis by manipulation of dietary fatty acids accelerates the development of glucocorticoid hypertension. Forty-eight rats were placed on either a 2-series prostaglandin 'inhibitory' diet (cod liver oil/linseed oil) or a control diet of saturated fat for an initial period of 4 weeks. The groups were then divided into two so that half of each received dexamethasone in their drinking water (2.5 mg/l) for 1 week whilst continuing their respective dietary regimens. Rats on the cod liver oil diet incorporated eicosapentaenoic acid into tissue stores with a corresponding decrease in arachidonic acid, and significantly impaired ability to generate serum thromboxane B2 (33%), aortic 6-oxo-prostaglandin F1 alpha (44%), renal homogenate prostaglandin E2 (45%) and 6-oxo-prostaglandin F1 alpha (74%) and urinary prostaglandin E2 (84%) and 6-oxo-prostaglandin F1 alpha (79%). Despite the diminished levels of vasodilator 2-series prostaglandins, the cod liver oil diet prevented the development of glucocorticoid induced hypertension. Relative to their respective dietary controls, dexamethasone treatment resulted in decreased serum thromboxane B2 (20%) but increased aortic 6-oxo-prostaglandin F1 alpha (186%), renal homogenate prostaglandins (127-230%) and urinary excretion of prostaglandin E2 (640-860%) and 6-oxo-prostaglandin F1 alpha (230-365%) in both dietary groups. It therefore seems unlikely that glucocorticoid induced hypertension is a consequence of inhibition of vasodilator prostaglandin synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acids; Body Weight; Dexamethasone; Dietary Fats; Dinoprostone; Fatty Acids; Fish Oils; Hypertension; Kidney; Male; Phospholipids; Prostaglandin Antagonists; Prostaglandins E; Rats; Rats, Inbred Strains; Renin; Thromboxane B2

To study the influence of dietary modification of prostaglandin synthesis on blood pressure regulation, the effects of dietary enrichment with linoleic acid were compared with standard rat chow in three groups of 24 rats before and after renal artery constriction and contralateral nephrectomy. Dietary supplementation with 40 energy% sunflower seed oil or linseed oil respectively caused incorporation of linoleic or linolenic acids into tissue phospholipids. Relative to the sunflower seed oil, the linseed oil diet led to inhibition of prostanoid synthesis in kidney, serum or aorta in vitro and urine in vivo. Rats on both oil-rich diets had lower blood pressures than rats on a standard diet. Thus, partial suppression of prostaglandin synthesis did not accelerate one-kidney, one clip Goldblatt hypertension, nor did sunflower oil protect against hypertension in a way that could be specifically ascribed to changes in prostaglandin synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; alpha-Linolenic Acid; Animals; Aorta; Blood Pressure; Body Weight; Dietary Fats; Fatty Acids; Hypertension, Renovascular; Kidney; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Prostaglandins; Rats; Thromboxanes

Extreme hyperglycemia (350 mg/dl) in rats results from streptozocin injection (50 mg/kg) and leads to a reduced aortic capacity for prostacyclin synthesis. Other complications such as hyperlipemia and alterations in body weight gain (loss or no gain) that might be responsible for the altered aortic prostacyclin synthesis occur concurrently. We injected neonatal rats (2 days of age) with intraperitoneal streptozocin to induce chronic mild diabetes (mean plasma glucose, 241 mg/dl) characterized in adult rats by normal body weight gain, normolipemia, and a physical appearance virtually indistinguishable from controls. Plasma insulin levels were reduced in rats with mild diabetes rats to 66% of control levels. A group of control and diabetic rats were given a 0.5% cholesterol diet for 7 weeks to induce hyperlipemia. Rats with diabetes and control rats given the cholesterol diet had elevated plasma insulin levels of 32% and 51%, respectively, and no alteration in plasma glucose levels (compared with respective controls), suggesting a state of insulin resistance. Aortic synthesis of 6-keto-PGF1 alpha from endogenous arachidonic acid was reduced in rats with mild diabetes and normolipemia or hyperlipemia. In contrast, the aortic conversion of exogenous arachidonic acid to 6-keto-PGF1 alpha was reduced only in rats with mild diabetes and hyperlipemia. Our results demonstrate that: (1) aortic prostacyclin synthesis is reduced in mild diabetes in the absence of alteration in plasma lipid levels and body weight gain; (2) aortic prostacyclin synthesis from endogenous arachidonic acid is more sensitive to diabetes than synthesis from exogenous arachidonic acid; (3) dietary cholesterol induces a state similar to insulin resistance and interacts with mild diabetes, resulting in reduced aortic prostacyclin synthesis from exogenous arachidonic acid.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Blood Glucose; Body Weight; Cholesterol; Cholesterol, Dietary; Diabetes Mellitus, Experimental; Epoprostenol; Insulin; Rats; Rats, Inbred Strains; Streptozocin; Triglycerides

Isolated rat aortae were perfused with Krebs buffer in vitro and the synthesis of prostacyclin-like material (PGI2-L) was continuously monitored by measuring the contraction of a superperfused rat stomach strip exposed to the aortic perfusate. PGI2-L release was high after initiation of the aorta perfusion but then gradually declined and stabilized at a basal rate of production that was maintained for at least 180 min. Levels of 6 keto prostaglandin F1 alpha(6ketoPGF1 alpha), the stable breakdown product of PGI2, in the aortic perfusate reflected the changes in biological activity. The concentration of PGE2 in the aortic perfusate remained constant throughout the experiment while the level of thromboxane (Tx)B2 (the stable product of TxA2) decreased with time to below the level of detection of the radioimmunoassay (RIA) used. All biological activity was abolished by heating the aortic perfusate for 30 min at 37 degrees C, while perfusing with 30 microM indomethacin inhibited aorta PGI-L formation. Analysis (by linear regression) of the relationship between PGI2-L formation and the body weight or age of the animals used revealed that PGI2-L synthesis was better related to body weight (r2 = 0.90) than age (r2 = 0.75).

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Aorta; Biological Assay; Body Weight; Epoprostenol; In Vitro Techniques; Indomethacin; Kinetics; Male; Muscle, Smooth, Vascular; Perfusion; Rats; Rats, Inbred Strains

Indomethacin and sulindac were used as tools to study the role of renal and/or systemic prostaglandins in the pharmacological response to atenolol. Patients receiving chronic treatment with atenolol 100 mg received indomethacin 50 mg twice daily or sulindac 200 mg twice daily in a randomised crossover trial. Indomethacin significantly reduced the antihypertensive action of atenolol while sulindac had no effect. The role that systemic and/or renal prostaglandins may play in the antihypertensive action of atenolol is discussed with reference to renal PGI2 production and inhibition of platelet cyclo-oxygenase.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Atenolol; Blood Pressure; Body Weight; Drug Interactions; Female; Humans; Hypertension; Indenes; Indomethacin; Male; Middle Aged; Random Allocation; Renin; Sulindac; Thromboxane B2

The effect of zinc deficiency on prostaglandin synthesis in rat testes was determined by feeding three groups of rats egg white-based semipurified diets. One group (ZD) was fed a zinc-deficient diet and two control groups were pair-fed (PF) or fed ad libitum (AL) a zinc-sufficient diet. The concentration (nanograms/gram) of the prostacyclin metabolite, 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha), in the tunica homogenate was significantly lower in ZD than in PF and AL groups. However, there was no difference when 6-keto-PGF1 alpha concentration was expressed as nanograms/milligrams of tunica protein. Tunica PGE2 concentrations (nanograms/gram) were not significantly altered by zinc deficiency. Concentrations of prostaglandins (PGs) in testis parenchyma were slightly higher in ZD probably as a result of increased levels of the precursor, arachidonic acid (AA). There was a highly significant correlation between PGE2 and AA in parenchyma phospholipids. PG synthesis was much greater in the tunica than in the parenchyma and prostacyclin appeared to be the major PG synthesized in both the tunica and parenchyma. It was concluded that PG synthesis is altered in the testes of zinc-deficient rats probably due to changes in concentrations of protein in the tunica and AA levels in parenchyma lipids.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Diet; Dinoprostone; Male; Organ Size; Prostaglandins; Prostaglandins E; Proteins; Rats; Rats, Inbred Strains; Testis; Zinc

The relationship between the renin-angiotensin system (RAS) and prostacyclin (PGI2) biosynthesis was studied in experimental diabetic rats. The group with diabetes induced by streptozotocin (STZ, 3.3 mmol/kg i.v.) showed prolonged hypertension, and plasma renin activity decreased markedly from 8.4 +/- 0.7 to 2.4 +/- 0.3 and 1.2 +/- 0.3 ng angiotensin I/ml per h at 2 and 8 weeks after STZ treatment. Plasma PGI2, determined as 6-keto-PGF1 alpha, decreased significantly at 8 weeks, with the values for the STZ-treated and control groups being 1490 +/- 99 and 2210 +/- 90 pg/ml, respectively. Significant suppression of renin release from renal cortical slices was observed at 8 weeks in the diabetic group, although no significant change was found in the renal renin content when compared with that of the controls. The release of PGI2 from the renal medullary slices of the diabetic group was suppressed at 2 and 8 weeks, with the suppression in aorta and renal cortical slices being apparent only at 8 weeks. These results indicate that suppression of the RAS may be related to PGI2 biosynthesis in diabetes mellitus.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Epoprostenol; Hypertension; Male; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acids; Blood Glucose; Body Weight; Cholesterol, Dietary; Diabetes Mellitus, Experimental; Lipids; Male; Rats; Rats, Inbred Strains

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Thoracic; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diet, Reducing; Insulin; Kinetics; Male; Rats; Rats, Inbred Strains