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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL033997-01
Application #
3346472
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1985-09-30
Budget End
1986-09-29
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of South Florida
Department
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
Gomez-Sanchez, E P; Fort, C; Thwaites, D (1992) Central mineralocorticoid receptor antagonism blocks hypertension in Dahl S/JR rats. Am J Physiol 262:E96-9
Gomez Sanchez, E P (1991) What is the role of the central nervous system in mineralocorticoid hypertension? Am J Hypertens 4:374-81
Gomez-Sanchez, E P; Fort, C M; Gomez-Sanchez, C E (1990) Intracerebroventricular infusion of RU28318 blocks aldosterone-salt hypertension. Am J Physiol 258:E482-4
Gomez-Sanchez, E P; Venkataraman, M T; Thwaites, D et al. (1990) ICV infusion of corticosterone antagonizes ICV-aldosterone hypertension. Am J Physiol 258:E649-53
Gomez Sanchez, E P (1988) Dose-response studies of intracerebroventricular infusion of aldosterone in sensitized and non-sensitized rats. J Hypertens 6:437-42
Gomez-Sanchez, E P; Gomez-Sanchez, C E (1988) 19-Nordeoxycorticosterone excretion in male and female inbred salt-sensitive (S/JR) and salt-resistant (R/JR) Dahl rats. Endocrinology 122:1110-3
Margo, C E; Gomez-Sanchez, E P; Gstalder, R (1987) Hereditary cataracts in the John Rapp inbred strain of Dahl salt-sensitive rat. Invest Ophthalmol Vis Sci 28:1422-8