The primary goal of my work is to determine the nature of the interactions between the hormone systems that govern pressure and volume homeostasis. To date, this work has focused on the renin-angiotensin-aldosterone system. Specifically, we have determined that renal sympathetic nerve activity is an essential, possibly the dominant, signal for renin secretion by the kidney.

Ongoing projects include:

1. An investigation of the renal histopathologic changes that occur in primary aldosteronism which may contribute to the 60% rate of persistent hypertension after removal of the functioning adenoma. One preoperative marker for failure of surgical cure of hypertension is the inability to completely suppress renin secretion, suggesting that preglomerular arteriolar nephrosclerosis contributes to its pathogenesis. Our studies integrate preoperative measurements of renin system physiology with intrarenal renin gene expression and renal histopathology from biopsy specimens obtained during unilateral adrenalectomy in patients with primary aldosteronism.

2. An assessment of the genes encoding 11-b-hydroxylase and 18-hydroxylase in functioning adrenal adenomas producing elevated levels of 18-methyl oxidation metabolites of cortisol in patients with primary hyperaldosteronism. An abnormal chimeric gene has been identified as the cause of glucocorticoid remediable aldosteronism in which these metabolites are also elevated. One issue is whether a related mutation might also account for their overproduction in primary hyperaldosteronism.

3. An evaluation of the effects of aldosterone on ventricular remodeling in patients with hypertension. The primary focus of this work will be to test the hypothesis that aldosterone, rather than angiotensin, is an independent stimulus for ventricular hypertrophy.