INTERRELATION BETWEEN RENIN MESSENGER-RNA LEVELS, RENIN SECRETION, AND BLOOD-PRESSURE IN 2-KIDNEY, ONE-CLIP RATS

To examine the interrelation between renin mRNA levels, renin secretio n, and blood pressure in rats, we clipped the left renal arteries of r ats and measured renin mRNA levels in both kidneys, plasma renin activ ity, and blood pressure. One and 2 days after clipping, renin mRNA lev els increased 3-fold and 4.3-fold in the stenosed kidney and were supp ressed to 52% and 26% of controls in the intact kidneys; plasma renin activity increased from 8 to 16.5 and to 30.5 ng angiotensin I.h(-1).m L(-1) and systolic blood pressure rose from 114 to 123 and to 137 mm H g. We found a strong correlation (P<.001) between plasma renin activit y and renin mRNA levels in the clipped kidneys. We also found signific ant correlations (P<.05) between mRNA levels in the clipped and intact kidneys and between plasma renin activity and blood pressure for the individual animals. Treatment of normal rats with the converting enzym e inhibitor ramipril (5 mg/kg twice a day) for 2 days increased renin mRNA levels in both kidneys fourfold. In animals with unilateral clips , additional treatment with ramipril increased renin mRNA levels 6.4-f old in the stenosed and 3.3-fold in the intact kidneys. These findings suggest that endogenous angiotensin II exerts an inhibitory effect on renin mRNA expression in normal kidneys, clipped kidneys, and their c ontralaterals. Suppression of the renin gene in contralateral kidneys seems not to be directly mediated by the rise of plasma renin activity or by the rise of blood pressure in two-kidney, one clip rats.