thromboxane-b2 and Weight-Gain

To assess age- and exercise-related changes in platelet aggregation, we measured the magnitude of platelet aggregation with a four-channel aggregometer, plasma and aortic polyunsaturated fatty acids by gas chromatography and related prostanoids with a reagent kit in young and aged non-exercised and in aged exercised rats.. Platelet aggregation in platelet-rich plasma induced by ADP (5 microm) in the primary wave increased with age. In the non-exercised groups, the basal levels of thromboxane B2 in platelet-rich plasma increased in aged rats compared with young rats. In aged exercised rats, the basal levels of 6-keto-prostaglandin F1alpha in platelet-rich plasma were stimulated and those of thromboxane B2 were depressed, compared with non-exercised aged rats. The plasma levels of eicosapentaenoic acid and docosahexaenoic acid increased with age. Only aortic eicosapentaenoic acid in the aged group increased by exercise. In the aged non-exercised and exercised groups, the aortic, but not the plasma, levels of eicosapentaenoic acid correlated inversely with the basal levels of thromboxane B2 in platelet-rich plasma (r = -0.53, P < 0.05) and associated negatively with the magnitudes of platelet aggregation induced by ADP (5 microm) (r = -0.47, P < 0.05).. These findings suggest that exercise in aged rats increases aortic eicosapentaenoic acid concentrations, which in turn depress the basal levels of thromboxane, B2 in platelet-rich plasma to modulate platelet aggregation.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Aging; Animals; Aorta; Chromatography, Gas; Docosahexaenoic Acids; Eicosapentaenoic Acid; Energy Intake; Fatty Acids, Unsaturated; Female; Immunoenzyme Techniques; Physical Conditioning, Animal; Platelet Aggregation; Rats; Rats, Wistar; Thromboxane B2; Weight Gain

The cardiovascular effects of a partially purified extract of fish oil, enriched in the n-3 series fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were studied in stroke-prone spontaneously hypertensive rats (SHR-SP) fed with high- and low-sodium diets during 5 weeks. Addition of salt to the low-salt control diet at a level commonly found in human food items (6% NaCl of the dry weight of the diet) produced a remarkable rise in blood pressure, an increase in left ventricular weight-to-body weight ratio (LVH-index) and an increase in kidney weight-to-body weight ratio (RH-index). Fish oil (20% of the dry weight of the diet) did not significantly influence the blood pressure or LVH-index or RH-index during the low-salt control diet. However, fish oil completely prevented the remarkable rise in blood pressure and clearly antagonized the rise of both LVH- and RH-indices, induced by the high-salt diet. The fish oil supplementation increased the levels of the polyunsaturated fatty acids of the n-3 series and decreased those of the n-6 series in plasma and kidney, irrespective of the salt content of the diet. Fish oil lowered serum thromboxane B2 concentration by approximately 75%. During the high-salt diet, fish oil markedly decreased water intake and urine volume, and increased urinary sodium concentration by about 60%. Our findings show that, in addition to an antihypertensive effect, fish oil also decreases LVH and RH. These effects appear to be due to an improved ability to excrete sodium and could be explained by the observed changes in the fatty acid composition and metabolism.

Topics: Animals; Eating; Fatty Acids; Fish Oils; Hypertension; Hypertrophy, Left Ventricular; Kidney; Male; Rats; Rats, Inbred SHR; Sodium Chloride, Dietary; Thromboxane B2; Weight Gain

Wistar rats (4-week-old) were administered with streptozotocin (45 mg/kg) through tail veins. After 3 months, diabetic rats were divided into 2 groups. One group (EPA group, n = 16) was fed a lipid-free diet (90%, w/w) plus lard (8%) and 90% pure eicosapentaenoic acid ethyl ester (2%) for 6 months. The other group (control group, n = 16) was fed in the same way except that eicosapentaenoic acid ethyl ester was replaced by safflower oil. Twenty-four-hour urine was collected just before starting the experimental diets and during the 6-month experimental period at monthly intervals. There were no differences in food intake and body weight between the two groups throughout the experiment. The mean microalbuminuria of the EPA group became significantly lower than that of the control group after 4 months on the diets through the end of the study (6 months). The mean microalbuminuria levels at the end of the study were 1.38 mg/day in the EPA group (n = 9) and 5.19 mg/day in the control group (n = 6) (p < 0.01). Eicosapentaenoic acid administration might retard the progression of diabetic nephropathy by reducing microalbuminuria.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Eating; Eicosapentaenoic Acid; Fatty Acids; Kidney; Lipids; Male; Organ Size; Rats; Rats, Wistar; Thromboxane B2; Weight Gain

The influence of a diet supplemented with MaxEPA (a fish oil concentrate, rich in eicosapentaenoic acid = EPA) on bleeding time in small mesenteric arteries of the rat and on formation of thromboxane B2 (TXB2) by ADP-stimulated platelets was investigated. Since EPA has been found to antagonize noradrenaline (NA) - induced vasoconstriction, the influences on bleeding time of the alpha-receptor antagonist phentolamine and of the adrenergic neuron blocking agent guanethidine alone as well as during dietary supplementation with MaxEPA were studied. Bleeding time slowly increased during the MaxEPA diet over a period of 12 weeks resulting in a final prolongation of about 75%. Indomethacin which dose-dependently increased bleeding time in control rats, further increased the already prolonged bleeding time in rats on the MaxEPA diet. Guanethidine prolonged bleeding time strongly in control animals but caused no further increase in those on the MaxEPA diet. Indomethacin also further increased the bleeding time prolonged by guanethidine, just as it did in animals on MaxEPA diet. In contrast to guanethidine, phentolamine prolonged bleeding time only slightly. The ability of platelets from rats on the diet to generate TXB2 was reduced to 59.5% but was more drastically reduced (to 26.7%) from rats pretreated with indomethacin. The results indicate that MaxEPA feeding prolongs bleeding time by a mechanism other than that of indomethacin. We speculate that EPA prolongs bleeding time rather by antagonizing the vasoconstrictor effect of sympathetic transmitters at the site of the injured vessel than by a reduced formation of TXA2.

Topics: Animals; Bleeding Time; Blood Platelets; Diet; Eicosapentaenoic Acid; Female; Fish Oils; Guanethidine; Indomethacin; Phentolamine; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Rats; Rats, Inbred Strains; Sympathomimetics; Thromboxane B2; Vasoconstriction; Weight Gain

The injection of 25 mg/kg i.p. cyclosporin (CsA) for 3 wk caused marked functional and morphological deteriorations of pancreatic islet cells in Wistar rats that were prevented by the combined administration of p-aminobenzoic acid-N-D-mannoside sodium salt (K-MAP). In this article, the toxic effect of CsA on pancreatic islet cells and the preventive effect of K-MAP on CsA-associated islet cell toxicity were investigated. Prolonged hyperglycemia and depressed insulin secretion after the glucose challenge observed in CsA-treated rats could be prevented by the combined administration of 300 and 900 mg/kg K-MAP. Cytoplasmic vacuolizations and a decrease in the number of mitochondria, intact endoplasmic reticula, secretory granules, and insulin-positive cells, as revealed by peroxidase-antiperoxidase staining, could also be prevented by the administration of 900 mg/kg K-MAP. This preventive effect of K-MAP on CsA-associated islet cell toxicity may suggest the combined use of K-MAP with CsA in pancreas transplantation and treatment of insulin-dependent diabetes.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Animals; Cyclosporins; Drug Interactions; Islets of Langerhans; Male; Mannose; Microcirculation; para-Aminobenzoates; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2; Weight Gain

Male young rats were fed 8% corn oil diets supplemented either with 2% phosphatidylinositol (PI) from safflower seeds or soybean lecithin (SL) for 22 days. Other groups of rats were fed 10% corn oil diets with or without (control) 0.3% inositol (IN, equivalent to the inositol moiety of the PI diet). The plasma cholesterol level was low in the SL group whereas liver triglyceride was low in all supplemented groups. The aortic production of prostacyclin tended to be high in rats fed the control diet and low in rats fed the SL diet, the PI and IN groups being intermediate. The concentration of plasma thromboxane B2 was comparable among various groups. In plasma and liver phosphatidylcholine, the ratio of arachidonate/linoleate was low in rats fed SL and high in rats fed PI or IN diets. The results indicate that, in addition to SL, the inositol moiety of PI may have a significant role in the regulation of lipid metabolism.

Topics: Adipose Tissue; Animals; Aorta; Cholesterol; Dietary Fats; Epoprostenol; Fatty Acids; Glycine max; Lipid Metabolism; Lipids; Liver; Male; Organ Size; Phosphatidylcholines; Phosphatidylinositols; Rats; Rats, Inbred Strains; Safflower Oil; Thromboxane A2; Thromboxane B2; Weight Gain