Enhanced adrenal renin and aldosterone biosynthesis during sodium restriction in TGR (mREN2)27

Abstract

The aim of the study was to investigate the relationships between tissue renin and the steroid production in the adrenal cortex during dietary sodium restriction in the transgenic rat (TGR) (mREN2)27. Thus the effects of a 1-wk low-sodium intake (0.04% NaCl) were studied in 5-wk-old male TGR (n = 33, systolic blood pressure = 151 +/- 3 mmHg) and in 24 age- and sex-matched outbred normotensive Sprague-Dawley (SD) rats. Measurements of plasma and tissue hormones were obtained at 0, 4, and 7 days of a low-sodium diet. Sodium restriction caused sustained increases of adrenal renin activity (from 28.5 +/- 3.5 to 87.5 +/- 4.5 ng.mg protein-1.h-1 on day 7) and of adrenal renin mRNA (+63 +/- 13 and +43 +/- 7% on days 4 and 7, respectively), whereas plasma renin activity (from 3.3 +/- 0.3 to 4.4 +/- 0.6 ng.ml-1.h-1) and renal renin activity (from 0.85 +/- 0.25 to 0.7 +/- 0.4 microgram.mg protein-1.h-1) did not change. The stimulation of the adrenal renin-angiotensin system was associated with a large increase of the aldosterone synthase cytochrome P-450 mRNA (+165 +/- 35 and +184 +/- 44%, on days 4 and 7) and of plasma aldosterone levels (from 125 +/- 32 to 338 +/- 59 pg/ml, P < 0.01). In SD rats, in spite of a more consistent increase in renal and circulating renin, mineralocorticoid production did not increase significantly. These results demonstrate that the exaggerated biosynthesis of aldosterone in TGR during sodium restriction is associated with an activation of renin in the adrenal cortex but not in the kidney.