The mechanisms by which mineralocorticoids elevate the blood pressure is still controversial. Direct and/or indirect pressor effects of mineralocortoicoids within the central nervous system have been postulated. The evidence gathered has been indirect. We have recently demonstrated that the intracerebroventricular infusion of aldosterone 5 ng/hr over 4 weeks induces a significant elevation of the blood pressure within 10 days. The subcutaneous infusion of the same dose has not effect on blood pressure demonstrating a CNS effect of aldosterone. I propose to expand upon and furhter characterize this model of hypertension. Studies to be done include a dose response to ICVT of aldosterone and evaluating the need for unilateral and nephrectomy and the effect of sodium loading and depletion in the development of this form of hypertension. The hypertensinogenic effect of the ICVT infusion of other mineralocorticoids including DOC and 9a-flurocortisol will be compared. To define the importance of central effect of the mineralocorticoid in hypertension induced by sytemically administered aldosterone we will infuse the antagonist prorenone into the lateral ventricle of the rat brain while infusing hypertensinogenic dose of aldosterone systemically. Prevention or reversal of the hypertension induced by aldosterone by ICVT prorenone will support the hypothesis that CNS centers are important in mineralocorticoid hypertension.
