Effect of glucocorticoid administration early in life on aortic prostaglandin synthesis and morphology in atherosclerosis-susceptible pigeons.

Effect of dexamethasone administration on aortic morphology, cholesterol content and synthesis of prostaglandins from (14C)-arachidonic acid in aorta of spontaneously atherosclerosis susceptible pigeons was examined. Dexamethasone markedly inhibited the synthesis of prostaglandin E2 and stimulated the synthesis of prostaglandin I2 in aorta. In aorta of glucocortocoid treated animals, endothelial abnormalities noted in control birds were decreased and numerous surface protrusions or 'microvilli' were noted. The possibility that glucocorticoid induced inhibition of PGE2 synthesis in pigeon aorta may contribute to improved aortic morphology is discussed.

Decreased atherogenic response to dietary cholesterol in pigeons after stimulation of cholesterol catabolism in early life.

Cholesterol catabolism was stimulated in 6-wk-old White Carneau pigeons using a laboratory stock diet containing 1.3% cholestyramine resin. After 8 wk on this diet the animals were returned to control stock diet (no resin) for another 8-wk period. When subsequently challenged with a diet containing 0.5% cholesterol, cholestyramine-pretreated pigeons exhibited significantly lower serum cholesterol level when compared with controls and this "hyporesponder" behavior persisted throughout the study period. Furthermore, the aorta of cholestyramine-treated animals exhibited significantly (a) lower prevalence and severity of atherosclerosis and (b) lower cholesterol content. These studies demonstrate for the first time that enhancement of cholesterol catabolism in early life improves resistance to diet-induced atherosclerosis in later life in this avian model.

Effect of testosterone and oxandrolone on thrombocyte aggregation and synthesis of prostaglandins in thrombocytes and aorta of atherosclerosis-susceptible pigeons.

Effect of intramuscular administration (10 mg/kg/week) of testosterone and oxandrolone on a) thrombocyte aggregation and b) synthesis of prostaglandins from [14C]-arachidonic acid in thrombocytes and aorta of atherosclerosis-susceptible White Carneau pigeon was examined. Neither testosterone nor oxandrolone influenced collagen, ADP and arachidonic acid induced aggregation or the synthesis of prostaglandins in thrombocytes. However, both testosterone and oxandrolone stimulated (p less than 0.05) the synthesis of 6-keto-PGF1 alpha (stable product of prostacyclin) und PGE2 in aorta.

Regional aortic differences in atherosclerosis susceptibility. Relationship to lipid concentration and prostaglandin biosynthesis.

In spontaneously atherosclerosis-susceptible White Carneau pigeons intimal cushions are noted consistently at the coeliac branch of aorta at birth. While these cushions do not progress into atherosclerotic lesions, the area across from the cushion (so called "lesion area") develop a classic atherosclerotic plaque by three years of age. In order to explain this regional aortic susceptibility to atherosclerosis, cholesterol and cholesteryl ester concentrations and prostaglandin biosynthesis in the two aortic regions were examined. It was found that the concentration of free and esterified cholesterol was higher in the intimal cushion area. Examination of the formation of various prostaglandins from C14-arachidonic acid indicates a striking increase in PGE2 synthesis in the lesion area with no difference in the formation of 6-keto PGF1 alpha (stable product of PGI2). These studies suggest that one of the earliest changes noted in the "lesion area" that differs from the intimal cushion is the enhanced formation of PGE2.

Regional aortic differences in atherosclerosis-susceptibility: changes in prostaglandin biosynthesis and cholesterol accumulation in response to desoxycorticosterone (DOCA)-salt induced hypertension.

In spontaneously atherosclerosis-susceptible White Carneau pigeons, intimal cushions that appear at birth near the coeliac branch of aorta do not progress into atherosclerotic lesions. However, the area across from the intimal cushion (so called 'lesion area') a) accumulates cholesteryl esters b) synthesizes more PGE2 and c) eventually develops into complicated atherosclerotic plaques. When DOCA-salt hypertension is induced in the pigeons, the 'initimal cushion' area displays a) accumulation of increasing amounts of cholesteryl esters and b) increase in the synthesis of all prostaglandins (particularly PGE2) from C14-arachidonic acid and c) approaches similarity to the 'lesion area' in the magnitude of these changes. These results suggest that under the influence of a risk factor, the 'intimal cushion' can acquire biochemical properties of the atherogenic areas of the aorta.