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.