Role of endogenous endothelins in the renin system of normal and two-kidney, one clip rats.

Abstract

This study aimed to investigate the relevance of endogenous endothelins in the control of renin secretion and renin gene expression under basal conditions and stimulated conditions achieved with unilateral renal artery stenosis. To this end, we studied the effects of the orally active endothelin antagonist Ro 47-0203 (100 mg/kg per day) for 2 days on plasma renin activity and renal renin mRNA levels in normal rats and rats with unilateral renal artery clips (0.2 mm). Treatment with Ro 47-0203 did not change basal arterial pressure but significantly attenuated the rise of blood pressure in response to renal artery clipping. Although Ro 47-0203 tended to increase basal plasma renin activity, this effect was not significant. Basal renin mRNA levels of kidneys were also not changed by the drug. Unilateral renal artery clipping increased plasma renin activity from 12 to 34 ng angiotensin I/mL per hour, increased renin mRNA levels to 328% of controls in the clipped kidneys, and decreased renin mRNA levels to 23% of controls in the contralateral intact kidneys. These changes were not influenced by Ro 47-0203. In isolated perfused rat kidneys, Ro 47-0203 (10 mumol/L) also had no effect on basal renin secretion or vascular resistance, but it substantially attenuated the decrease of renin secretion and renal flow in response to administration of exogenous endothelin. Taken together, these findings suggest that endogenous endothelins play no relevant role in the control of renin secretion and of renin gene expression in normal and hypoperfused rat kidneys.