Comparison of the Effects on Renin Release of Beta Adrenergic Antagonists with Differing Properties

Abstract

A B S T R A C T Continuous 6-h infusions of the beta adrenergic blockers dl-propranolol or oxprenolol significantly reduced plasma renin activity (PRA) and mean blood pressure in the resting rabbit and prevented the stimulatory effects of isoproterenol on renin release and heart rate. These actions were due to blockade of beta receptors, for the inactive isomer, d-propranolol, had no effect. Despite sustained high plasma concentrations of dl-propranolol (0.2 Ag/ml) in the unstimulated animal, PRA did not fall below 36% of control values, suggesting that basal renin secretion is maintained partly by factors other than beta adrenergic mechanisms.Prindolol, another beta blocker, also abolished the effects of isoproterenol on renin and on the heart, and reduced blood pressure in the resting animal. However, prindolol increased resting PRA and heart rate, and in animals already receiving dl-propranolol, it raised PRA and heart rate without further altering blood pressure. This suggests that the effect on PRA of prindolol was due to its intrinsic sympathomimetic activity and not hypotension-mediated mechanisms. The observation that the blood pressure-lowering effect of prindolol was associated with a rise in PRA, while another beta antagonist, H 35/25, lowered PRA but had no effect on blood pressure, indicates that the hypotensive action of beta blockers is unrelated to their effects on renin release.In both unstimulated and isoproterenol-challenged animals, only blockers possessing beta-i receptor affinity (d,t-propranolol, oxprenolol, prindolol, practolol, and metoprolol) affected heart rate, while effects on PRA were more prominent with agents possessing beta-2 activity (dl-propranolol, oxprenolol, prindolol, and H 35/25). Thus, the changes in PRA caused by the beta adrenergic blockers appear to be dependent upon the summation of their direct effects, antagonistic or sympathomimetic, on beta-2 adrenergic receptors regulating renin release.

Effects of beta 1‐adrenoceptor agonism on plasma renin activity in normal men.

“…On the other hand predominant 813-adrenoceptor blocking agents such as atenolol (Amery et al, 1976) and metoprolol (Lijnen et al, 1979) are able to inhibit the renin secretion. However, selective ,82-adrenoceptor blockers, have been shown to antagonize the secretion of renin provoked by isoprenaline and to be more powerful than non-selective and selective j1-adrenoceptor blockers in these experimental models (Weber et al, 1974;Imbs et al, 1977). The latter results together with the findings of the present study could indicate that ,81-adrenoceptors are either not at all or only to a minor extent involved in the modulation of the secretion of renin.…”

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

“…Moreover, the infusion of the beta agonist, isoproterenol, may not be comparable to any beta adrenergic properties of renal nerve stimulation. Lastly, previous studies claiming to support the existence of an intrarenal beta adrenergic receptor influencing renin release have not considered the membrane stabilizing (anesthetic) property of d,l-propranolol (20,21). The present experimental protocol was designed to avoid these above objections.…”

“…If this were the case, then the inhibitory effect of dl-propranolol on renin release might have resulted from the effects of the drug on renal hemodynamics or sodium excretion. Moreover, the d-isomer of propranolol, which is devoid of beta adrenergic inhibitory properties, is a potent membrane stabilizer (20,21). The possibility exists, therefore, that this property of dl-propranolol accounted for its ability to impair renin release.…”

An INVESTIGATION INTO THE TYPE OF Β‐ADRENOCEPTOR MEDIATING SYMPATHETICALLY ACTIVATED RENIN RELEASE IN THE CAT

“…In other experiments stimulation of the renal nerves at a rate which caused almost identical changes in renal blood flow (Coote etal., 1972;Johns & Singer, 1974a) resulted in renin release, almost all of which could be blocked by propranolol. Thus, in the study of Weber et al (1974) blockade of these indirect actions of isoprenaline by the P2-adrenoceptor antagonists could well have accounted for their greater effectiveness in blocking renin release and therefore led to the suggestion of P2-adrenoceptors mediating renin release.…”

“…This was supported by an in vitro study (Johns, Richards & Singer, 1975) which showed that both selective and non-selective 3-adrenoceptor agonists could stimulate renin release from cat isolated renal cortical cells. In another study Weber, Stokes & Gain (1974) (1978) and Desaulles, Meisch & Schwartz (1978) concluded that, in rats Pl-adrenoceptors were involved in sympathetically-mediated renin release from the kidney. Similarly, studies both in conscious dogs (Himori, Izumi & Ishimori, 1980) and in anaesthetized dogs (Kopp, Aurell, Nilsson & Ablad, 1980) demonstrated that adrenergic renin release was probably mediated by Pl-adrenoceptors.…”