Studies are proposed to measure blood pressure chronically in different rat models of obesity and test the hypothesis that blood pressure becomes evaluated by changes in baroreflex sensitivity, cardiovascular reactivity, regional hemodynamics, or humoral regulation. Initial experiments will determine whether blood pressure becomes progressively elevated as rats gain weight following chemical or electrolytic lesions of the ventromedial hypothalamus, or prolonged feeding of high-fat and high-sugar diets, and compare the chronic time course of blood pressure changes with that occurring in Zucker """"""""fatty' and Koletsky obese SHR rats. If hyperphagia occurs during induction of obesity in any of the models being studied, effects of diets containing reduced salt will be compared to determine how much of the change in blood pressure is due to salt loading. Subsequently, other experiments will study effects of dietary caloric restriction on blood pressure changes occurring in the various rat models in order to explore the possibility that reduction in body weight would alleviate hypertension as it does in man. Since hyperinsulinemia commonly occurs in all obese rat models, its contribution to the associated hypertension will be assessed by using subdiabetogenic doses of streptozotocin or alloxan to reduce pancreatic insulin secretion. If significant elevations of blood pressure are detected in obese rats, terminal experiments will be done to determine whether changes in baroreflex sensitivity, cardiovascular reactivity, or regional hemodynamics contribute to the ensuing hypertension. Finally, other terminal experiments will also assess the extent to which sympathetic, vasopressin, and renin-angiotensin pressor mechanisms participate in regulating blood pressure in obese rats. By obtaining basic information on what happens to blood pressure in obese rats, these studies may identify models that would allow detailed examination of mechanisms underlying obesity hypertension.
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