Effects of Aldosterone and Spironolactone on Arterial Renin in Rats

Abstract

1.The metabolic role of arterial angiotensin I-forming enzyme (i.e. renin activity) was studied in total homogenates and in subcellular fractions of the aorta of normotensive and hypertensive rats.2. Angiotensin I-forming enzyme was measured in (a) uninephrectomized rats rendered hypertensive with D-aldosterone and sodium chloride (10 g/l) drinking solution, (b) rats treated in the same manner but with the addition of spironolactone, and (c) control rats.3. Hypertension developed in aldosterone-treated rats within 3-6 weeks and was associated with decreased plasma and renal renin values. Total aortic renin activity was up to sixfold higher in the hypertensive animals than in control animals and there was an increased ratio of supernatant to microsomal renin activity in the aorta.4. In spironolactone-treated rats blood pressure and total aortic renin concentrations were comparable with those in the control rats.5. The results support the hypothesis that renin generated at local vascular sites, which is independent of circulating renin levels, contributes to regulation of blood pressure.

Aldosterone Antagonism in Chronic Kidney Disease

“…In the remnant kidney model of CKD, ACE inhibitors and ARB attenuate renal injury (13). Other animal models, including radiation nephritis (16), cyclosporine toxicity (17), diabetes (18), obstruction (19), and other models of hypertension (20,21), implicate aldosterone in the pathogenesis of progressive kidney disease. These results support a direct role for the mineralocorticoid in promoting renal disease.…”