An effect of extrarenal beta adrenergic stimulation on the release of renin.

The present study was undertaken to examine whether the beta adrenergic agonist, isoproterenol, increases plasma renin activity (PRA) by activation of intrarenal or extrarenal pathways. The effects of intravenous (i.v.) and renal arterial infusion of isoproterenol on PRA and renin secretion rate (RSR) were compared in anesthetized dogs. In 12 studies in 9 dogs i.v. infusion of isoproterenol (0.009-0.018 mug/kg per min) was associated with an increase in PRA from 14.7 to 35.7 ng/ml per 3 hr (P < 0.001). PRA decreased to 19.4 ng/ml per 3 hr (P < 0.001) after cessation of the infusion. In innervated kidneys RSR increased from 1640 to 5062 U/min (P < 0.02) and decreased to 2132 U/min after cessation of the infusion (P < 0.05). In denervated kidneys the control RSR was significantly lower (455 U/min) but still increased during i.v. infusion of isoproterenol to 2762 U/min (P < 0.001) and decreased to 935 U/min (P < 0.001) after the infusion was stopped. These changes in PRA and RSR were associated with an increase in cardiac output averaging 49% and a large decrease in total peripheral resistance. These effects of i.v. isoproterenol to increase RSR were not mediated by changes in renal perfusion pressure since this was held constant by adjusting a suprarenal aortic clamp. In addition, there were no changes in glomerular filtration rate, renal plasma flow, or electrolyte excretion in either denervated or innervated kidneys during i.v. infusion of isoproterenol, and the concentration of potassium in plasma was unchanged. Prior hypophysectomy abolished the antidiuretic effect of i.v. isoproterenol but did not prevent the effect on RSR. In contrast, renal arterial infusion of isoproterenol at the same dose had no apparent effect on PRA and RSR in seven studies in five dogs and also did not produce changes in cardiac output, peripheral resistance or renal hemodynamics. These results do not provide evidence for a role of intrarenal beta adrenergic receptors in the control of renin release and indicate that the effect of beta adrenergic stimulation with isoproterenol to increase the release of renin is mediated by an extrarenal mechanism. Since the effect of i.v. isoproterenol occurred in the absence of changes in plasma potassium concentration, renal perfusion pressure, glomerular filtration rate, renal plasma flow, and electrolyte excretion and was not abolished by renal denervation, the possibility must be considered that the effect on renin secretion is mediated by circulatory factors. The changes in systemic hemodynamics which occurred with i.v. but not renal arterial infusion of isoproterenol may be involved in the initiation of such a pathway.