This research program addresses the hypothesis that dietary constituents have a significant effect on blood pressure (BP), a major cardiovascular risk factor, in subgroups of hypertensives. It is a collaborative effort among investigators with expertise in circulatory control, autonomic function, platelet function, intestinal transport, thermogenesis and energy balance, and obesity modification. Project I - Hypothesis: Increasing oral Ca++ intake lowers BP in patients with essential hypertension (HBP); this alteration is dependent on sodium intake. The effect of varying Ca++ and Na+ intake in essential hypertensives, stratified by renin status and Na+ sensitivity, will be assessed with multivariate analysis of the possible independent effects of alterations in Na+ in serum total and ionized Ca++ and parathyroid hormone. We will determine intraplatelet Ca++, Na+, platelet function and peripheral vascular reactivity in patients. Intestinal Ca++ absorption and handling in SHR and Ca++ transport in red cell ghosts from hypertensive subjects. Project II - Hypothesis: Methylxanthines, particularly dietary caffeine, have a deleterious effect in patients with renovascular hypertension (RV HBP). Studies in a RV animal model in our laboratory suggest that caffeine causes such a serious increase in BP that malignant HBP supervenes. Determination of renal vein renin, angiotensin, and adenosine levels during infusions of placebo and methylxanthine in patients with RV HBP will allow us to define whether caffeine's effect is mediated by enhanced renin release as a result of its adenosine receptor inhibition. Allied studies in SHR will define possible interactions between Na+ and caffeine. Double-blind, placebo-controlled caffeine trials in patients with RV HPB and in individuals with renin levels raised by low sodium diets will be performed. Project III - Hypothesis: Dietary modification in obese hypertensives may have differential effects on vascular reactivity and BP, depending on the fatty acid (FA) constituents of the weight reduction diet. Clinical studies of BP modification by weight reduction diets will be done utilizing omega-6, omega-3, and saturated FAs. In patients receiving omega-3 FAs, studies of platelet function and platelet incorporation of these FAs will help define potential additional beneficial effects on cardiovascular risk. Studies of peripheral vascular reactivity will be perormed in these subjects at the initation and termination of the weight reduction period.
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