The long-term objectives of the research proposed in this application are to establish the relationships between modification of dietary lipids and cardiovascular function. We and others have recently demonstrated the antihypertensive property of fish oils in relevant animal models of hypertension: One of the mechanisms responsible for the antihypertensive action is likely mediated through changes in the activity of the sympathetic nervous system. Previous studies demonstrated that dietary fat modification may promote changes in alpha- and beta-adrenoceptor number and affinity; membrane cholesterol (C)/phospholipid (PL) ratios; central and peripheral sympathetic nervous system activity; and vascular smooth muscle function via effects on synthesis of vasodilators.
The specific aims of this project are to examine the effects and potential mechanisms of action of omega-9, omega-6 and omega-3 unsaturated fatty acids on 1) blood pressure and heart rate, 2) plasma and cardiac lipid composition and C/PL ratios, 3) sympathetic nervous system activity determined by norepinephrine turnover in the heart, kidney, adrenal medulla and brain, and 4) cardiac membrane alpha- and beta-adrenoceptor number and affinity. Semi-purified diets supplemented with varying amounts of beef tallow, olive oil, corn oil, fish oil and combination of purified eicosapentaenoic and docosahexaenoic acid ethyl esters will be fed to spontaneously hypertensive and Wistar Kyoto rats from 4 to 14 weeks of age. Systolic blood pressure will be determined by a tail-cuff method, plasma and cardiac membrane lipid compositions by thin-layer chromatography and gas chromatography procedures, catecholamines by HPLC with electrochemical detection, and alpha- and beta-adrenoceptor density by ligand binding in the presence and absence of antagonists. This proposed project will further our understanding of the effects and molecular mechanisms of action of different types of dietary lipids on cardiovascular function which in turn will permit us to gain new insight into the role of dietary lipids in maintenance of optimal human health.
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