Effect of beta adrenergic blockade on renin response to renal nerve stimulation.

Abstract

A B S T R A C T The ability of dl-propranolol to block renin secretion in response to various extrarenal stimuli, such as hemorrhage and hypoglycemia, has been interpreted to indicate the presence of an intrarenal beta receptor regulating renin release. However, two problems complicate this interpretation: (a) the stimuli have effects outside the kidney, and (b) dl-propranolol has a local anesthetic, as well as a beta adrenergic blocking, action. In the present study, the effects of a purely intrarenal stimulus, in the form of renal nerve stimulation (RNS), on renin secretion was examined. The effects of dl-propranolol (anesthetic and beta-blocking activity), l-propranolol (beta-blocking activity only), and d-propranolol (local anesthetic activity only) on the renin response to RNS were examined. In a control group of animals, two sequential RNS increased mean renin secretion from 401 to 1,255 U/min (P < 0.25) and from 220 to 2,179 U/min (P <0.01). In a second group the first RNS increased renin secretion from 201 to 1,181 U/min (P < 0.01), but after dl-propranolol was given RNS did not significantly alter renin secretion (33 to 55 U/min). In a third group the initial RNS increased renin secretion from 378 to 1,802 U/min (P < 0.025), but after l-propranolol was given RNS had no significant effect on renin secretion (84 to 51 U/min). A fourth group of dogs showed a rise in renin secretion from 205 to 880 U/min (P < 0.001) in response to the first RNS, while the second RNS, given after an infusion of d-propranolol, caused a rise in renin secretion from 80 to 482 (P < 0.005). The nature of the electrical stimulus was consistent in all groups and caused no detectable changes in renal or systemic hemodynamics or in urinary electrolyte excretion. The results, there-

Mechanisms of portal hypertension-induced alterations in renal hemodynamics, renal water excretion, and renin secretion.

“…Since GFR and RBF decreased in these innervated kidneys during elevations in PVP, activation of either the baroreceptor or macula densa mechanisms or both may have been involved in the enhanced rate of renin secretion. However, in a recent study from our laboratory, we have been able to dissociate the effect of renal nerve stimulation on renin secretion from changes in GFR, RBF, and solute excretion (26). This effect of renal nerve stimulation to stimulate renin secretion was abolished by l-propranolol, a beta adrenergic blocker, but not by d-propranolol, a membrane-stabilizing agent.…”

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

“…Sympathetic activation results in activation of the RAS (Reid, 1992), and renin release is inhibited by ␤-blockers (Assaykeen et al, 1970;Pettinger et al, 1973;O'Malley et al, 1975;Proakis et al, 1989). Although renin secretion was stimulated through intrarenal ␤-receptors independent of changes in systemic or renal hemodynamics or in tubular sodium reabsorption, treatment with a ␤-blocker, propranolol, inhibited renin secretion induced by renal nerve stimulation (Taher et al, 1976). An additive effect of ␤-blockade with RAS blockade to reduce microalbuminuria was observed in the analysis of a prespecified secondary endpoint of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial .…”

Mechanisms of Renin Secretion during Hemorrhage in the Dog

“…The study of renin secretion has been particularly enigmatic when a stimulus such as hemorrhage has been employed to provoke renin release; this may be true because hemorrhage may represent a heterogenous stimulus to renin release. For example, hemorrhage may induce renin secretion through activation of arterial stretch receptors in the renal circulation when renal perftision pressure (RPP)l falls (1,2); similarly, an increase in renal sympathetic nerve activity (3,4) or an increase in circulating catecholamines (5-7) may also induce renin secretion. Finally, a decrease in sodium delivery to the macula densa may occur with hemorrhage and thus provide another efferent mechanism for renin release (8).…”