Complications from untreated essential hypertension (HT) represent the number one killer today in the United States. In an attempt to understand the mechanisms responsible for the development of HT in humans, many investigators have turned to research with animal models. Although a great deal has been learned, there have been few studies which address environmental variables and the role that various factors, such as diet, exercise, stress, etc. are believed to play in HT in humans. The relative paucity of such studies reflects the absence of an appropriate model, one which becomes hypertensive only following exposure to the appropriate environmental factors. Recently, a rat model has been developed which shows considerable promise for such studies. The present proposal seeks to begin to study the mechanisms responsible for this environmentally-induced HT. Specifically, the first study seeks to characterize the role the lateral hypothalamus plays in stress-induced HT in rats with one hypertensive parent by lesioning this structure. In a second study, animals with no, one, or two hypertensive parents will be exposed to high sodium diet, cutaneous electric shock stress, neither or both. Although a host of questions will be addressed by this study, the primary one is whether there are any discrete CNS changes in catecholamines and their metabolites consequent to these interventions, and as a function of genetic background. In a third study, the acute reactivity of rats with no, one, or two hypertensive parents will be compared. The goal of this study is to gain information which will eventually attempt to relate acute reactivity to chronic blood pressure elevations. In a fourth study, the development of chronic stress-induced HT will be delineated by measuring cardiac output, total peripheral resistance, and blood pressure in chronically stressed animals. In a fifth study, the role of the baroreceptors in stress-induced HT will be studied utilizing phenylephrine curves, sinoaortic denervation and light microscopic studies of the carotid arteries. With regard to exercise, there are three proposed studies. The first seeks to determine if any CNS hypothalamic or brainstem catecholaminergic nuclei important in cardiovascular function are affected by exercise training, which virtually prevents the development of stress-induced HT. The second will compare the adaptation of blood pressure responses to shock stress in exercise-trained and untrained animals. Finally, the last study seeks to study the effect of nucleus fastigius lesions on cardiovascular adaptations to exercise training.
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