dinoprost and Hyperlipidemias

Isoprostanes are emerging as a new class of biologically active products of arachidonic acid metabolism of potential relevance to human vascular disease. Their formation in vivo seems to reflect primarily, if not exclusively, a nonenzymatic process of lipid peroxidation. Enhanced urinary excretion of 8-iso-PGF2 alpha has been described in association with cardiac reperfusion injury and with cardiovascular risk factors, including cigarette smoking, diabetes mellitus, and hypercholesterolemia. Besides providing a likely noninvasive index of lipid peroxidation in these settings, measurements of specific F2 isoprostanes in urine may provide a sensitive biochemical end point for dose-finding studies of natural and synthetic inhibitors of lipid peroxidation. Although the biological effects of 8-iso-PGF2 alpha in vitro suggest that it and other isoeicosanoids may modulate the functional consequences of lipid peroxidation, evidence that this is likely in vivo remains inadequate at this time.

Topics: Antioxidants; Arteriosclerosis; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Free Radicals; Gas Chromatography-Mass Spectrometry; Humans; Hyperlipidemias; Immunoassay; Indicator Dilution Techniques; Lipid Peroxidation; Oxidative Stress; Platelet Aggregation; Prostaglandins F; Risk Factors; Thrombosis; Vasoconstrictor Agents

Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear.. The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high-oleic acid meals; the secondary objective was to characterize the effects of linoleic acid-enriched high-fat meals relative to the control meal.. We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high-oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high-linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35-70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L).. Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0-3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse-reflection index was not significantly different. Plasma 8-isoprostane F2α analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed.. These data show differential postprandial 8-isoprostane F2α responses to high-fat meals containing EPA + DHA-rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid-derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Dietary Fats; Dinoprost; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fish Oils; Humans; Hyperlipidemias; Male; Meals; Middle Aged; Nitric Oxide; Oleic Acids; Plant Oils; Postprandial Period; Sunflower Oil; Triglycerides

Postprandial lipaemia impairs endothelial function, possibly by changes in oxidative stress, but whether this affects cardiac output and/or systemic vascular resistance (SVR) at rest and in response to dynamic exercise remains uncertain. The present study set out to investigate the effects of a high-fat meal (HFM) v. a low-fat, high-carbohydrate meal (HCM) on cardiac output and SVR. A HFM (50 g fat) and an isoenergetic HCM (5 g fat) were randomly fed to thirty healthy adults using a crossover design. Cardiac output, heart rate and blood pressure (BP) were measured, and stroke volume and SVR were calculated over a 3 h rest following the meal, during exercise 3 h postprandially and for 45 min post-exercise. Blood samples were collected at fasting, 3 h postprandially and immediately post-exercise. Plasma TAG increased by 63.8 % 3 h following the HFM, and NEFA fell by 94.1% 3 h after the HCM. There was a 9.8% rise in plasma 8-isoprostane-F2alpha concentration following the HFM, and a 6.2% fall following the HCM. Cardiac output increased postprandially, but the difference between meals at rest or exercise was not statistically significant. The HFM resulted in a 3.2 mmHg (95% CI 0.7, 5.7) smaller increase in exercise mean arterial BP compared with the HCM due to a greater fall in exercise SVR. Postprandial lipaemia induced by a HFM does not affect cardiac output and/or SVR at rest, but it blunts the increase in BP during exercise.

Topics: Adult; Blood Pressure; Cardiac Output; Cross-Over Studies; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Dietary Carbohydrates; Dietary Fats; Dinoprost; Exercise; Female; Heart Rate; Hemodynamics; Humans; Hyperlipidemias; Male; Postprandial Period; Single-Blind Method; Stroke Volume; Triglycerides; Vascular Resistance; Young Adult

Rosuvastatin, a strong statin, and colestimide, a new anion exchange resin, are both clinically beneficial drugs for treatment of hypercholesterolemia. The main purpose of the study was to compare the effects of rosuvastatin and colestimide on metabolic parameters, adipokines, and markers of oxidative stress and diabetic nephropathy in patients with type 2 diabetes complicated by hyperlipidemia.. A total of 40 patients with type 2 diabetes complicated by hyperlipidemia were recruited prospectively and consecutively. The patients were assigned randomly in equal numbers to rosuvastatin (2.5 mg/day) and colestimide (3.0 g/day) groups. Blood and urine tests were performed at the beginning of the study and after 12 weeks.. Rosuvastatin significantly decreased the level of serum retinol-binding protein (RBP)-4, an insulin-resistant adipokine, in a subgroup of patients with poor glycemic control, in addition to exerting a strong low-density lipoprotein (LDL-C)-lowering effect. Colestimide significantly decreased HbA1c, even in patients treated with a sulfonylurea at a more than moderate dose, without influencing insulin resistance or adiponectin (an insulin-sensitive adipokine) and RBP4. Colestimide also significantly decreased the levels of urinary 8-iso-prostaglandin (PG) F2alpha (a marker of oxidative stress) and urinary monocyte chemoattractant protein-1 (MCP-1) (a marker of diabetic nephropathy).. Our results show that rosuvastatin and colestimide exert different beneficial effects in type 2 diabetic patients complicated by hyperlipidemia. Therefore, concomitant use of these drugs may be useful for prevention of progression of diabetic complications.

Topics: C-Reactive Protein; Chemokine CCL2; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dinoprost; Enzyme-Linked Immunosorbent Assay; Epichlorohydrin; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Imidazoles; Male; Middle Aged; Oxidative Stress; Peptide Fragments; Prospective Studies; Pyrimidines; Resins, Synthetic; Retinol-Binding Proteins; Rosuvastatin Calcium; Sulfonamides

Hemodialysis patients have uremic dyslipidemia, represented by elevated serum intermediate-density lipoprotein cholesterol (IDL-C) levels, and an increased cardiovascular mortality rate. This study was performed to determine the low-dose effects of the angiotensin II receptor blocker losartan and the angiotensin-converting enzyme inhibitor trandolapril on pulse wave velocity (PWV), which predicts cardiovascular morbidity and mortality in hemodialysis patients.. Serum lipid levels and PWV were monitored for 12 months in 64 hemodialysis patients who were administered low doses of losartan or trandolapril or a placebo.. At the start of the study, there were no differences in patient characteristics among the 3 groups. PWV tended to increase in the placebo group during the 12-month study period, but decreased significantly in the losartan and trandolapril groups, and decreases in PWV were similar in the losartan and trandolapril groups. There were no changes in blood pressure, hematocrit, erythropoietin dose, ankle-brachial index, serum lipid levels, serum 8-isoprostane levels, or serum C-reactive protein levels during the 12-month study period, but there was an increase in serum triglyceride levels in the losartan group and a decrease in serum IDL-C levels in the losartan and trandolapril groups.. In hemodialysis patients, trandolapril is as effective as losartan in decreasing PWV independent of its depressor effect and in suppressing elevated IDL-C levels. Long-term blockade of the renin-angiotensin system may have a beneficial effect on the acceleration of atherosclerosis and uremic dyslipidemia.

Topics: Aged; Anemia; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Comorbidity; Dinoprost; Drug Therapy, Combination; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Hyperlipidemias; Indoles; Kidney Failure, Chronic; Lipids; Lipoproteins; Lipoproteins, LDL; Losartan; Male; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome; Vascular Resistance

Despite the potential benefits of dietary treatment with marine omega3 fatty acids in cardiovascular disease, there remains concern with respect to their potential for increased lipid peroxidation. Thus far, data from in vivo studies are inconclusive. Increased lipid peroxidation has also been associated with acute exercise in some studies, but the methods have been nonspecific. The quantitation of F2-isoprostanes provides a more reliable and useful assessment of in vivo lipid peroxidation. We therefore aimed to assess the independent and combined effects of dietary omega3 fatty acids and aerobic exercise training on urinary F2-isoprostane levels in dyslipidemic non-insulin-dependent diabetic (NIDDM) patients. In a randomized controlled trial, 55 untrained, sedentary, dyslipidemic NIDDM patients were randomly assigned to a low-fat diet (30% of daily energy) with or without one daily fish meal (3.6 g omega3 fatty acids per day) and further randomized to either a moderate (55% to 65% maximal oxygen consumption [VO2max]) or light (heart rate <100 bpm) exercise training program for 8 weeks. Twenty-four-hour urine samples from 49 subjects were collected for measurement of urinary F2-isoprostanes by gas chromatography-mass spectrometry before and after intervention. The fish diets reduced urinary F2-isoprostanes by 830+/-321 pmol/24 h (20%, P = .013) relative to the low-fat diet alone. This effect was independent of age, gender, and body weight change. Moderate exercise training did not alter F2-isoprostanes. These findings show that, at least in the short-term, exercise had no effect, whereas the inclusion of regular fish meals as part of a low-fat diet reduced in vivo lipid peroxidation in dyslipidemic NIDDM patients. This response could further complement the known benefits of omega3 fatty acids and exercise favoring a reduced cardiovascular risk in diabetic patients.

Topics: Adult; Aged; Animals; Diabetes Mellitus, Type 2; Dietary Fats; Dinoprost; Exercise; Female; Fishes; Humans; Hyperlipidemias; Male; Middle Aged; Treatment Outcome

Oxidative stress may increase the risk of atherosclerosis. The association of mild forms of hyperlipidemia, particularly primary hypertriglyceridemia, with oxidative stress has not been fully investigated. The aim of this study was to assess the alterations in oxidative stress biomarkers associated with three major types of mild untreated hyperlipidemia (hypercholesterolemia, hypertriglyceridemia and combined hyperlipidemia) in nonsmoker and smoker individuals. Five biomarkers were measured in 139 adult healthy men (83 nonsmokers and 56 smokers, ages 18-75), which included normolipidemic and hyperlipidemic subjects. Triglyceride levels were associated with a significant main effect on ferric reducing antioxidant power (FRAP) and 8-iso-prostaglandin F2α (iPF2α) levels in plasma (p<0.05 and p<0.005, respectively). Smokers with hypercholesterolemia, hypertriglyceridemia and combined hyperlipidemia had alterations in 1, 3 and 2 oxidative stress biomarkers compared to nonsmoker normolipidemics. Smokers (including normolipidemics and hyperlipidemics) had higher plasma FRAP (120.8 vs. 102.0 μM quercetin/l, p<0.05) and erythrocyte catalase activity (5125 vs. 4093 U/g Hb, p<0.01), while they had lower erythrocyte glutathione peroxidase activity (20.3 vs. 23.0 U/g Hb, p<0.05) compared to nonsmokers. These findings show that mild forms of hyperlipidemia, particularly in smokers, are associated with alterations in some oxidative stress biomarkers.

Topics: Adolescent; Adult; Aged; Biomarkers; Catalase; Dinoprost; Glutathione Peroxidase; Humans; Hyperlipidemias; Male; Middle Aged; Oxidative Stress; Smoking; Superoxide Dismutase; Young Adult

Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E-deficient mice.. Six-month-old male apolipoprotein E-deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure.. Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II-driven AAA formation in hyperlipidemic mice.

Topics: Angiotensin II; Animals; Antioxidants; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Rupture; Apolipoproteins E; Blood Pressure; Dinoprost; Hyperlipidemias; Lipids; Macrophages; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Mutant Strains; Osteopontin; Oxidative Stress; Sialoglycoproteins; Vasoconstrictor Agents; Vitamin E

Postprandial lipaemia is known to cause endothelial dysfunction, but its underlying mechanism is still under debate. The present study was undertaken to investigate the effects of postprandial lipaemia on endothelial dysfunction and oxidative stress. We measured plasma glutathione peroxidase (GSH-Px), an antioxidant enzyme, and the urinary excretion of 8-epi-prostaglandin F2alpha (8-PGF2alpha), a free radical-catalysed product from the oxidative modification of arachidonic acid, in 16 healthy subjects (mean age, 30 +/- 5 years) without major coronary risk factors. Plasma high-sensitive C-reactive protein, soluble intercellular cell-adhesion molecule-1 and vascular cell-adhesion molecule-1 were also measured. High-resolution ultrasound was used to assess the flow-mediated vasodilatation (FMD) of the brachial artery. Blood and urine samples were collected before and 2, 4 and 6 h after a standard high-fat meal (3677 J, containing 50 g of fat). Serum triacylglycerol (triglyceride) increased and FMD decreased significantly after a high-fat meal. Plasma GSH-Px significantly decreased from 27.2 +/- 12.3 microg/ml to 25.7 +/- 11.8 microg/ml (P=0.022) 2 h after the meal, and urinary excretion of 8-PGF2alpha significantly increased from 1286 +/- 1401 pg/mg of creatinine to 2197 +/- 1343 pg/mg of creatinine (P=0.014) at 4 h after the meal. However, there were no significant changes in the levels of high-sensitive C-reactive protein and adhesion molecules after a high-fat meal. In conclusion, endothelial dysfunction was observed after consuming a high-fat meal and is associated with augmented oxidative stress manifested by the depletion of serum antioxidant enzymes and increased excretion of oxidative modification products.

Topics: Adult; Analysis of Variance; Biomarkers; Brachial Artery; C-Reactive Protein; Dietary Fats; Dinoprost; Endothelium, Vascular; Glutathione Peroxidase; Humans; Hyperlipidemias; Intercellular Adhesion Molecule-1; Male; Oxidative Stress; Postprandial Period; Regional Blood Flow; Triglycerides; Ultrasonography; Vascular Cell Adhesion Molecule-1

It is well known that free radicals contribute to endothelial dysfunction and are involved in ageing and in the pathogenesis and development of many cardiovascular diseases, such as atherosclerosis. Measurement of F(2)-isoprostanes has emerged as probably the most reliable approach to assess oxidative stress status in vivo. In particular, 8-isoprostane (8-epiPGF(2alpha)) has been indicated as a marker of antioxidant deficiency and oxidative stress of potential relevance to assess human vascular diseases.. To provide evidence for enhanced oxidative stress in coronary artery disease (CAD).. Plasma levels of 8-epiPGF(2alpha) (EIA, Cayman Chemicals, Ann Arbor, Michigan, USA) were measured in 51 patients (19 females, 32 males, age: 58.7+/-1.6 years, mean+/-SEM). Subjects included 13 healthy control subjects (group I), and 38 patients underwent coronary angiography; 11 patients without coronary artery atherosclerotic lesions (group II), and 27 with angiographically proven CAD (group III).. Plasma levels of 8-epiPGF(2alpha) were 123.2+/-9.5, 314.6+/-40 and 389.6+/-36.2 pg/ml in groups I, II and III respectively (P<0.05 and P<0.001 groups II and III versus group I, respectively). In group III, 8-epiPGF(2alpha) levels increased with the number of affected vessels (324.4+/-47.2 and 408.3+/-44.1 pg/ml for one- and multi-vessel disease, P=0.07 and P<0.001 versus control subjects, respectively). A significant difference in 8-epiPGF(2alpha) levels was observed between patients with and without hypertension (394.2+/-42.7 and 232.7+/-25.1 pg/ml, P<0.01, respectively). In addition, patients with dyslipidaemia presented higher 8-epiPGF(2alpha) levels with respect to non-dyslipidaemic patients (359.1+/-35.6 and 240.3+/-34.3 pg/ml, P<0.05, respectively). A positive relationship was found between age and 8-epiPGF(2alpha) levels (r=0.42, P<0.01) in the whole population.. These findings indicate that elevated levels of plasma 8-epiPGF(2alpha) levels are associated with the extent and the severity of coronary artery disease and with the occurrence of different atherogenic risk factors, supporting the hypothesis that the evaluation of oxidative stress may represent an additional prognostic predictor in such events and a potential target of future therapeutic interventions.

Topics: Aged; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Dinoprost; Evidence-Based Medicine; F2-Isoprostanes; Female; Humans; Hyperlipidemias; Hypertension; Italy; Male; Middle Aged; Oxidative Stress; Regression Analysis; Risk Factors; Smoking; Statistics as Topic

Topics: Adult; Anticholesteremic Agents; Atorvastatin; Dinoprost; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Isoprostanes; Lovastatin; Male; Middle Aged; Pravastatin; Pyrroles; Simvastatin; Smoking

The effect of hyperlipemia associated with diabetes on the contractility of resistance arteries to prostaglandin F2alpha (PGF2alpha) was investigated employing 4 weeks simultaneously hyperlipemic-diabetic (HD), hyperlipemic (H), diabetic (D) and normal hamsters (controls, C). The isometric force produced by explanted arteries in the presence of 10(-8) to 10(-5) M PGF2alpha was recorded by the myograph technique. The results showed that compared with controls, the contractile response to 10(-5) M PGF2alpha was approx. 2 fold increased in HD group, and approx. 1.75 and 1.62-fold enhanced in H and D groups, respectively. Activation of protein kinase C with 10(-6) M phorbol 12-myristate 13-acetate increased the contractility to PGF2alpha in all groups and particularly in HD hamsters (approx. 10.16-fold). Inhibition of cyclooxygenase by indomethacin increased approx. 1.81-fold the arterial contractility to PGF2alpha in C group, whereas in H, D and HD hamsters had no effect. Blockage of Ca(2+)-activated K(+)-channels with 10(-3) M tetraethylammonium augmented the contraction to PGF2alpha approx. 6.43-fold in C group, and at significantly lower levels in H, D and HD groups, i.e. approx. 3.84, 3.72 and 3.33-fold, respectively. The results validate two conclusions: (i) simultaneous insult of hyperlipemia-hyperglycemia is associated with the highest contractility of the resistance arteries to PGF2alpha; the highest circulating glucose and cholesterol levels, and the enhancement in the protein kinase C pathway underlay the augmented contractility; (ii) no matter the pathology induced (hyperlipemia, diabetes or both simultaneously) a common dysfunctional response to PGF2alpha was installed; this consists in a reduced effect of cyclooxygenase inhibition, and a altered activity of Ca(2+) dependent K(+) channels.

Topics: Aging; Animals; Blood Glucose; Cricetinae; Diabetes Mellitus, Experimental; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hyperlipidemias; Indomethacin; Male; Mesenteric Arteries; Mesocricetus; Potassium Channels, Calcium-Activated; Protein Kinase C; Tetraethylammonium; Time Factors; Vasoconstriction

The effects of fluvastatin on levels of urinary 8-iso-prostaglandin F2alpha (iPF2alphaIII), a marker of oxidative stress, and low-density lipoprotein (LDL) particle size in serum were investigated in patients with hypercholesterolemia. After 6 months of fluvastatin therapy, levels of urinary iPF2alphaIII decreased from 1720.1 +/- 392.0 to 539.6 +/- 75.5 pg/mg (p < 0.01), and LDL particle size increased from 24.3 +/- 0.3 to 26.5 +/- 0.2 nm (p < 0.001). These changes from the treatment of fluvastatin were not correlated with those of the serum LDL cholesterol (LDL-C) levels. The results imply that fluvastatin, with its unique antioxidant property among statins, reduces oxidative stress and increases LDL particle size simultaneously in hyperlipidemic patients.

Topics: Aged; Dinoprost; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Particle Size

The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity. When Sprague-Dawley rats (n=60) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (158+/-3.4 mm Hg systolic pressure), whereas the other half (obesity-resistant [OR] group) maintains a body weight equivalent to that of a low fat control group and is normotensive (135.8+/-3.8 mm Hg). We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid-reactive substances showed a significant increase in the LDL fraction of OP rats (2.8+/-0.32 nmol malondialdehyde/mg protein) compared with OR and control rats (0.9+/-0.3 nmol malondialdehyde/mg protein). Also, aortic and kidney thiobarbituric acid-reactive substances showed a significant (3- and 5- fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold increase in the OP group compared with both the OR and control groups. In addition, free isoprostane excretion and nitrotyrosine in the kidney showed an increase in OP rats only. The urine and plasma nitrate/nitrite measured by the LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However, endothelial NO synthase expression in the kidney cortex and medulla assessed by reverse transcriptase-polymerase chain reaction showed a strong increase in the OP rats versus OR and control rats (endothelial NO synthase/beta-actin ratio 1.3+/-0.04 in OP rats versus 0.44+/-0.02 in OR rats), suggesting a possible shift toward superoxide production by the enzyme. Collectively, the data show a decreased NO bioavailability in OP animals that is due in part to the increased oxidative stress.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Dietary Fats; Dinoprost; Disease Models, Animal; F2-Isoprostanes; Hyperlipidemias; Hypertension; Kidney Cortex; Kidney Medulla; Lipid Peroxides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Renin; Thiobarbituric Acid Reactive Substances

Isoprostanes (IP) are a new family of compounds formed during oxidation injury. 8-epi-prostaglandin (PG) F2alpha, a vasoconstrictory and mitogenic substance, is increased in hyperlipidemia in blood and urine as well as at the vascular level in the intima, in particular along foam cells. Similarly, cigarette smoking is associated with an immediate increase in 8-epi-PGF2alpha and a quick drop after quitting. Also diabetes and even the more a combination of risk factors (for the development of atherosclerosis) results in increased 8-epi-PGF2alpha in various compartments. Others, such as sex, age, hypertension and obesity were of minor influence. These findings further indicate, that in-vivo oxidation injury as reflected by increased IP may play a relevant role in atherogenesis. IP may serve as useful markers to assess oxidation injury at a local level.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticholesteremic Agents; Arteriosclerosis; Blood Component Removal; Blood Vessels; Child; Child, Preschool; Dinoprost; Female; Humans; Hyperlipidemias; Immunohistochemistry; Lipoproteins, LDL; Male; Middle Aged; Molecular Structure; Smoking; Thiobarbituric Acid Reactive Substances; Vasoconstrictor Agents

Prostacyclin (PGI2), thromboxane A2 (TXA2) and F2-isoprostanes, prostaglandin F2-like compounds, have wide and contrasting spectrum of biological activities and may influence blood pressure and atherogenesis. To investigate the dynamics of PGI2, TXA2 and F2-isoprostanes in patients with hypertension and hyperlipidemia (HH group), we measured the major urinary metabolites of PGI2: 6-keto PGF1alpha (Keto) and 2,3-dinor-6-keto PGF1alpha, (Dinor), those of TXA2:TXB2 and 11-dehydro TXB2 (Dehydro), and urinary 8-isoprostane (Iso) in 34 patients. Urinary excretion of Dinor was significantly lower in patients than in controls and that of Dehydro was significantly higher in patients than in controls. Keto, TXB2 and Iso were not significantly different between them. Antiplatelet agents decreased not only TXA2 metabolites but also PGI2 metabolites. Urinary C-peptide immunoreactivity was correlated with Dinor and Dehydro. After administration of eicosapentaenoic acid (EPA), total cholesterol (T-cho) and triglycerides (TG) significantly decreased. Although prostanoids did not show significant change, changes in T-cho were correlated with changes in Dinor and changes in Iso. These results suggest that PGI2 and TXA2 of systemic origin might be related to the pathophysiology of hypertension and hyperlipidemia and that the dynamics of PGI2, TXA2 and F2-isoprostanes might be related to not only blood pressure regulation but also lipid and glucose metabolism.

Topics: Aspirin; Dinoprost; Dipyridamole; Eicosapentaenoic Acid; Epoprostenol; Humans; Hyperlipidemias; Hypertension; Platelet Aggregation Inhibitors; Thromboxane A2; Ticlopidine

Topics: Biomarkers; Diabetes Mellitus, Type 2; Dinoprost; Gas Chromatography-Mass Spectrometry; Humans; Hyperlipidemias; Kidney Failure, Chronic; Reference Values

The hypolipidemic, antiatherogenic and thrombolytic effects and decrease of prostaglandin F2 alpha (PG) excretion were observed in 55 patients suffering from Ischemic heart disease, hyperlipidemia and hypertension fed the antiatherosclerotic diet containing 20 g of eiconol during 55 days. The low initial level of natural antibodies to PGF2 alpha was increased significantly in blood serum. Authors consider that decrease of PGF2 alpha level under diet influence is connected not only with the change of fatty acid composition of cell membranes but also with increasing of natural antibody production.

Topics: Adult; Aged; Diet, Atherogenic; Dietary Fats, Unsaturated; Dinoprost; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Immunity, Innate; Male; Middle Aged; Myocardial Ischemia

Clinicopathologic and histopathologic evidence of both endoperoxidation with hyperprostaglandinemia and hyperlipidemia in a 5-week-old infant with a hemophagocytic syndrome is reported. Institution of histiocytolytic (VP-16) and cyclo-oxygenase inhibitor (indomethacin) therapies returned the prostaglandin levels and lipid profile to a nearly normal state coincidental with clinical recovery. It appears that by reducing the cell mass of histiocytes and controlling the over-production of prostaglandins, some types of hemophagocytic syndrome can be reversed.

Topics: Dinoprost; Dinoprostone; Etoposide; Glucose; Histiocytes; Humans; Hyperlipidemias; Indomethacin; Infant; Lipid Peroxides; Liver; Lymphatic Diseases; Lymphocytosis; Male; Phagocytosis; Prostaglandins E; Prostaglandins F; Vitamin E