Hypertension is a known risk factor for cardiovascular disease. Abnormalities of renal function and body fluid regulation are common in both experimental and human hypertension. Three hormones vital to the maintenance of stable body fluid volume and composition -- i.e., angiotensin II, aldosterone and vasopressin -- also may importantly affect neural mechanisms controlling arterial pressure. Thus, the central hypothesis of the proposed work is that circulating hormones primarily engaged in regulation of body fluid homeostasis can chronically alter arterial pressure level by interactions with the central nervous system. Five specific hypotheses related to this central theme will be tested in conscious, chronically instrumented rats. 1) Physiologically relevant increments in plasm angiotensin II concentration cause a slowly-developing (days to weeks) increase in neurogenic vasoconstrictor tone. 2) Increases in plasma angiotensin II cause a sustained increase in plasma aldosterone; this increase in aldosterone is of sufficient magnitude to contribute to angiotensin-induced hypertension. 3) Chronic blockade of brain aldosterone receptors will attenuate both aldosterone- and angiotensin=induced hypertension. 4) Increases in plasma vasopressin, within a physiological range, will produce sustained hypertension in rats in which the sympathoinhibitory actions of the hormone are prevented. 5) Actions of angiotensin II and/or aldosterone -- possibly on the brain --contribute to hypertension development in the reduced renal mass form of experimental hypertension. These experiments will utilize long-term hormone infusion; and measurement of slat and water balance, systemic hemodynamics and plasma hormone levels in rats with either surgical or pharmacological manipulations designed to impair central/neural cardiovascular control processes. The ultimate goal of this work is to define the functional relationships between cardiovascular and body fluid regulatory mechanisms in the central nervous system.
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