WHICH FACTOR MEDIATES RENO-RENAL CONTROL OF RENIN GENE-EXPRESSION

Objective: To obtain information about possible pathways mediating the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys. Design: The effects of unilateral renal denervation and of treatment with an angiotensin II antagonist (losartan) on renal renin gene expression were examined in a two-kidney, one-clip model. Methods Renal renin messenger RNA levels, plasma renin activity, blood pressure and kidney weights were monitored over 10 days in adult male Sprague-Dawley rats with various unilateral reductions of renal blood flow achieved with silver clips of 0.2, 0.3 and 0.4 mm inner diameter . Results: With all the clip sizes used, renin messenger RNA levels in creased transiently in the clipped kidneys, the time course and the ma gnitude of the increase being dependent on the degree of flow reductio n. In the contralateral kidneys clipping caused sustained decreases in renin messenger RNA to levels proportional to the clip size. The supp ression of renin gene expression in the contralateral kidneys was not related to compensatory growth of the organs nor to changes in plasma renin activity or arterial pressure. Unilateral denervation of the kid ney before clipping had no influence on the characteristic increase an d decrease in renin messenger RNA in the stenosed and contralateral ki dneys, respectively. Treatment of the rats with losartan led to fourfo ld increases in renal renin messenger RNA levels and to sixfold increa ses in plasma renin activity in control rats. A 0.3-mm clip did not fu rther increase renin messenger RNA or plasma renin activity in losarta n-treated rats but again led to suppression of renin messenger RNA in the contralateral kidney to 50% of the levels found in the clipped kid neys. Conclusions: The results suggest that the suppression of renin g ene expression in the contralateral kidneys of stenosed kidneys is not due to compensatory renal growth nor mediated by systemic blood press ure, angiotensin II AT1 receptors or renal nerves. We therefore hypoth esize that kidneys with reduced perfusion release a humoral factor tha t acts as a potent inhibitor of renin gene expression.