Effect of beta-blocking agents and angiotensin II on isoproterenol-stimulated renin release from rat kidney slices.
Mechanisms by which beta-blocking agents decrease blood pressure and suppress renin release are incompletely understood. We previously demonstrated that renin release by kidney slices may be increased by beta-adrenergic agonists, and the present communication contains our results on the effects of 15 beta-blocking agents and angiotensin II on isoproterenol-stimulated renin release. None of the beta-blocking compounds inhibited basal renin release. Each agent was evaluated at concentrations ranging from 10-8 to 10-5 m and three different dose-response curve patterns were observed: (1) Metoprolol, acebutolol, labetalol, and d-propranolol had no effect on isoproterenol-stimulated renin release at any concentration, whereas pindolol and bufuralol demonstrated minimal inhibition at 10-5 m only. (2) Isoproterenol stimulation was completely inhibited when dl- or l-propranolol, alprenolol, and sotalol were administered at doses ranging between 5 x 10-6 and 10-6 m; but greater concentration of these agents resulted in reappearance of the isoproterenol response. (3) Dose-related inhibition was observed with practolol, oxprenolol, timolol, nadolol, and atenolol at concentrations ranging from 10-8 to 10-5 m. Basal renin release was significantly (P is less than 0.01) inhibited by angiotensin II at 10-6 m, which also inhibited isoproterenol-stimulated renin release in a dose-related fashion. [Sar1, Ala8] angiotensin II had no direct effects on either basal or isoproterenol-stimulated renin release, but blocked the inhibitory action of angiotensin II on these parameters.


CONCLUSIONS
There are three different effects of beta-blocking agents on isoproterenol-stimulated renin release which can only partially be explained by their presently ascribed pharmacological properties. (Beta 1- and beta2-agonists, intrinsic sympathomimetic activity, membrane-stabilizing actions). Angiotensin II inhibition of renin release appears to be functionally related to adrenergic pathways.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007545:Isoproterenol / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051381:Rats; D012083:Renin / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology; D000092502:Renin Inhibitors
D000319:Adrenergic beta-Antagonists; D000804:Angiotensin II; D007545:Isoproterenol; D012083:Renin; D012504:Saralasin; D000092502:Renin Inhibitors