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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.[1]


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