Role of Adrenal Renin in the Regulation of Aldosterone

Mulrow, Patrick

Abstract

A renin isoenzyme is found in the adrenal gland with the highest concentration in the zona glomerulosa cells. This renin isoenzyme has a molecular weight of about 40,000 daltons. In preliminary experiments, we found that the concentration of the enzyme increased following several days of a low sodium or high potassium diet and decreased with high sodium diet. After nephrectomy, the concentration increased markedly. These changes in zona glomerulosa renin correlated significantly with changes in aldosterone concentration. These physiological manipulations did not alter the renin concentration of the inner zone. In the present proposal, we plan to characterize further the adrenal renin by standard renin isolation techniques, determine if inactive renin is present, and localize the subcellular concentration of the renin by homogenization and centrifugation techniques and by immunofluorescent techniques using a monoclonal antibody specific for renin. After standardization of the adrenal renin method of measurement, we plan to investigate the role of adrenal renin in the regulation of aldosterone production. We will study the effect of acute and chronic sodium depletion, acute and chronic potassium loading and potassium depletion on adrenal renin and aldosterone. In view of the marked increase in adrenal renin post nephrectomy, we will study the role of potassium, ACTH and the pituitary, and angiotensin II feedback inhibition. Furthermore, by using converting enzyme inhibition in the nephrectomized rat, we will further define the relationship of renin to aldosterone. We will attempt to measure other components of the renin-angiotensin system in adrenal glomerulosa cells. The production of angiotensinogen, angiotensin II, and converting enzyme will be estimated. We will try to grow zona glomerulosa in tissue explant culture and, if successful, study the factors regulating adrenal renin production in vitro.