thromboxane-a2 and Weight-Gain

Vascular disease is a major cause of mortality and morbidity in chronic diabetes mellitus. Prostanoids, metabolites of arachidonic acid, include vasoactive substances produced and released from the vascular wall. Alterations in prostanoid production have been reported in the vasculature of diabetic humans and experimental animals. The aim of the present work was to study the influence of three different periods of long-term streptozotocin-induced diabetes, 30, 120 and 180 days in the production of prostanoids in the thoracic aorta and in the mesenteric vascular bed of the rat. The prostanoids released to the incubation medium by the tissues were extracted and measured by reversed-phase HPLC. In the diabetic groups, body weight was reduced and glycaemia was increased when compared with the corresponding non-diabetic controls. In the aorta, 30 days of diabetes did not modify the prostanoid release pattern, meanwhile 120 and 180 days of incubation decreased prostacyclin (PGI(2)) production. In the mesenteric bed, at 30 days the release of the vasodilators PGI(2) and prostaglandin (PGE(2)) and the vasoconstrictor thromboxane (TXA(2)) was reduced. At 120 days the vasodilators were reduced and at 180 days such reduction was joined by an increase of the release of vasoconstrictor metabolites. Thirty days of diabetes did not modify the PGI(2)/TXA(2) ratio in the aorta or mesenteric bed. On the other hand, 120 and 180 days of diabetes reduced significantly the ratio when compared with the corresponding controls. In conclusion, the mesenteric bed, a resistance vascular bed, seems to be more sensitive than the aorta, a conductance vessel, to the effects of diabetes on prostanoid production. The observed effects contribute to a displacement of the balance of prostanoid release in favour of the vasoconstrictor metabolites, a phenomenon that could be related to the vascular complications of diabetes mellitus.

Topics: Animals; Aorta; Blood Glucose; Chromatography, High Pressure Liquid; Diabetes Mellitus, Experimental; In Vitro Techniques; Male; Mesentery; Prostaglandins; Rats; Rats, Wistar; Splanchnic Circulation; Streptozocin; Thromboxane A2; Time Factors; Weight Gain; Weight Loss

The effect of dietary protein, either casein (CAS) or soybean protein (SOY), on the polyunsaturated fatty acid (PUFA) composition of liver microsomal phospholipids and eicosanoid production was compared in normal and streptozotocin-induced diabetic rats fed diets containing perilla oil rich in alpha-linolenic acid. In normal rats the linoleic acid desaturation index in liver microsomal phospholipids was significantly higher in the CAS group than in the SOY group, whereas it was reversed in diabetic rats. The proportion of eicosapentaenoic acid (EPA) decreased in diabetic rats, in particular those fed SOY, whereas it was vice versa for arachidonic acid (AA). The ratio of aortic prostacyclin production to platelet thromboxane A2 production decreased only in diabetic rats fed SOY reflecting a reduction of the EPA/AA ratio. Thus, dietary protein differently modified the PUFA composition and eicosanoid balance even in the diabetic rat. In this respect, alpha-linolenic acid seemed to be less influential than linoleic acid.

Topics: alpha-Linolenic Acid; Animals; Arachidonic Acid; Blood Glucose; Caseins; Diabetes Mellitus, Experimental; Dietary Fats, Unsaturated; Dietary Proteins; Eicosanoids; Eicosapentaenoic Acid; Epoprostenol; Fatty Acids, Unsaturated; Glucagon; Insulin; Linolenic Acids; Male; Microsomes, Liver; Phospholipids; Plant Proteins, Dietary; Rats; Rats, Sprague-Dawley; Soybean Proteins; Thromboxane A2; Weight Gain

Through an unknown mechanism, dimethyl sulfoxide (DMSO) retards atherogenesis in cholesterol-fed rabbits (CFR). We studied the effects on the development of lesions and prostacyclin (PGI2) production in the thoracic aorta and total serum lipid and cholesterol content of the abdominal aortic serum thromboxane (TXB2) and plasma fibrinogen levels in rabbits fed control versus atherogenic diets, with and without DMSO. Without DMSO, PGI2 production was significantly higher in CFR versus control animals (8.65 +/- 1.0 vs 6.38 +/- 0.3 ng/15 min [p less than 0.02]). DMSO did not influence PGI2 production in any of the groups but significantly reduced the number of atheromatous lesions in CFR (78% +/- 9% vs 8% +/- 4% [p less than 0.001]). With DMSO, CFR had a significant reduction in total lipid levels (422 +/- 5 vs 300 +/- 21 mg/gm dry wt [p less than 0.01]) and cholesterol levels (74 +/- 12.8 vs 31.8 +/- 6.4 mg/gm dry wt [p less than 0.01]) compared with control animals. Fibrinogen levels were significantly lower in CFR versus control animals (0.83 +/- 0.07 vs 2.42 +/- 0.13 mg/ml [p less than 0.01]). TXB2 was lower in DMSO plus control versus control animals alone. In conclusion, DMSO does not appear to act through changes in PGI2 or fibrinogen activity. Its effect in lowering TXB2 in CFR suggests an action on platelet function.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Cholesterol; Cholesterol, Dietary; Diet, Atherogenic; Dimethyl Sulfoxide; Drinking; Epoprostenol; Fibrinogen; Male; Rabbits; Thromboxane A2; Triglycerides; 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