ALDOSTERONE, HYPERTENSION AND THE BRAIN
Principal Investigator: Elise P Gomez-Sanchez
Abstract: DESCRIPTION: (Adapted from the Investigator's Abstract) Aldosterone is a powerful mineralocorticoid, which plays a significant role in the pathogenesis of several forms of human and experimental hypertension. In excess it is also responsible for direct deleterious effects on the heart, and cerebral and renal vasculature, independent of its effect on the blood pressure. The applicant has demonstrated that Aldosterone biosynthesis occurs in vascular tissues and the brain, in addition to the adrenal zona glomerulosa. The amount of aldosterone synthesis in the brain is very small, but it may have paracrine effects through receptors located within a short distance of its site of synthesis. They have published evidence supporting the action of central mineralocorticoids in the hypertension of the Dahl Salt-Sensitive rat. The concentration of aldosterone in the brain is higher than that in plasma, even in normal outbred rats. A significant proportion, approximately 2/3, occurs as low polarity acyl esters of aldosterone. Acyl esters of several steroids are reported to accumulate in the CNS. They found the presence of two different aldosterone acyl esters, an oleate, and what may be one of the three possible aldosterone monoactates isomers. Preliminary evidence suggests that acylation of aldosterone increases its biological activity in vivo. They propose the hypothesis that: Aldosterone action in brain is potentiated or prolonged by acylation. The specific aims to test this hypothesis are 1) Isolation and elucidation of the structures of acyl esters of aldosterone found in the brain. 2) Measurement of aldosterone acyl esters in the serum and specific areas of the brain in normal and pathophysiologic conditions. 3) Assessment of the hypertensinogenic activities of the aldosterone acyl esters. 4) Study of the metabolism of aldosterone and corticosterone and the regulation of the synthesis of low polarity derivatives in the brain, including the identification of the sites of formation of aldosterone acyl esters.
Funding Period: 1981-07-01 - 2005-03-31
more information: NIH RePORT
- Mineralocorticoid receptors in the brain and cardiovascular regulation: minority rule?Elise P Gomez-Sanchez
Research Service, G V Sonny Montgomery VA Medical Center and Department of Medicine, Division of Endocrinology, The University of Mississippi Medical Center, Jackson, MO, USA
Trends Endocrinol Metab 22:179-87. 2011..MR antagonists are valuable adjuncts to the treatment of chronic cardiovascular and renal disease; the crucial need to discover targets for development of selective therapy for specific MR functions is also discussed...
- Central regulation of blood pressure by the mineralocorticoid receptorElise P Gomez-Sanchez
Research Service, G V Sonny Montgomery VA Medical Center, 1500 Woodrow Wilson Dr, Jackson, MS 39216, USA
Mol Cell Endocrinol 350:289-98. 2012....
- Effect of 3beta-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive ratElise P Gomez-Sanchez
Research Service, G V Sonny Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA
Am J Physiol Regul Integr Comp Physiol 288:R389-93. 2005..These studies suggest that the synthesis in the brain of a mineralocorticoid receptor agonist, probably aldosterone, is responsible in part for the salt-induced hypertension of the inbred Dahl SS/jr rat...
- Is aldosterone synthesized within the rat brain?Elise P Gomez-Sanchez
Research Service, G V Sonny Montgomery VA Medical Center, 1500 E Woodrow Wilson Drive 151, Jackson, MS 39216, USA
Am J Physiol Endocrinol Metab 288:E342-6. 2005..It is postulated that the small amounts of aldosterone synthesized in the brain could provide a local ligand for autocrine or paracrine activation of the mineralocorticoid receptor...
- Central mineralocorticoid receptors and cardiovascular diseaseElise P Gomez Sanchez
Division of Endocrinology, University of Mississippi Medical Center, Jackson VA Medical Center, Jackson, MS 39216, USA
Neuroendocrinology 90:245-50. 2009..MR that pertain to the central modulation of cardiovascular function and health are addressed herein...