Role of renal nerves in the stimulation of the renin system by reduced renal arterial pressure.

The aim of this study was to determine the role of renal innervation in the prolonged stimulation of renin secretion and renin synthesis accompanying renal artery stenosis. Male Sprague-Dawley rats, in which the left kidney had been denervated or sham denervated 4 days earlier, received a left renal artery clip (ID 0.2 mm). Plasma renin activity and renin mRNA were assayed 1, 2, or 4 days after clipping. The stimulation of both plasma renin activity and renin mRNA was blunted markedly in the rats with the denervated clipped kidney. The typical suppression of renin mRNA in the intact right kidney, however, was not different between rats with sham-denervated or denervated left kidneys, nor was the increase of blood pressure in response to renal artery clipping different between the experimental groups. To test whether the suppression of renin mRNA in the contralateral kidney was related to the increase of blood pressure, another group of rats with denervated clipped left kidneys was treated additionally with the T-type calcium channel blocker mibefradil (15 mg. kg(-1). d(-1)). Despite blood pressure normalization by mibefradil, plasma renin activities and renin mRNA levels in the clipped denervated kidneys and in the intact right kidneys remained unchanged. These findings suggest that renal nerves are responsible for marked background stimulation of both renin secretion and renin mRNA expression, which is normally masked by the inhibitory effect of renal perfusion pressure on the renin system. Renal nerve activity is therefore an important determinant of the gain of renin stimulation during reduced renal arterial pressure.