ENHANCED ADRENAL RENIN AND ALDOSTERONE BIOSYNTHESIS DURING SODIUM RESTRICTION IN TGR (MREN2)27

The aim of the study was to investigate the relationships between tiss ue renin and the steroid production in the adrenal cortex during dieta ry 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, an d 7 days of a low-sodium diet. Sodium restriction caused sustained inc reases 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 ac tivity (from 3.3 +/- 0.3 to 4.4 +/- 0.6 ng.ml(-1).h(-1)) and renal ren in activity (from 0.85 +/- 0.25 to 0.7 +/- 0.4 mu g.mg protein(-1).h(- 1)) did not change. The stimulation of the adrenal renin-angiotensin s ystem 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 ren al and circulating renin, mineralocorticoid production did not increas e significantly. These results demonstrate that the exaggerated biosyn thesis of aldosterone in TGR during sodium restriction is associated w ith an activation of renin in the adrenal cortex but not in the kidney .