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(Hypertension. 1999;33:467-471.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effects of Vasodilatory ß-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

Masao Kakoki; Yasunobu Hirata; Hiroshi Hayakawa; Hiroaki Nishimatsu; Yasuko Suzuki; Daisuke Nagata; Etsu Suzuki; Kazuya Kikuchi; Tetsuo Nagano; Masao Omata

From the Second Department of Internal Medicine, Faculty of Medicine (M.K., Y.H., H.H., H.N., Y.S., D.N., E.S., M.O.), and Faculty of Pharmaceutical Sciences (K.K., T.N.), University of Tokyo (Japan).

Correspondence to Yasunobu Hirata, MD, The Second Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail hirata-2im{at}h.u-tokyo.ac.jp

Abstract—The mechanisms for the vascular actions of vasodilatory ß-blockers remain undetermined. For some kinds of ß-blockers, the involvement of nitric oxide (NO) has been suggested. We studied the effects of vasodilatory ß-blockers on renal perfusion pressure (RPP) and NO release in the rat kidney. Infusion of bopindolol, celiprolol, and nebivolol caused a dose-dependent reduction in RPP and an increase in NO release (RPP: bopindolol 10^-6 mol/L, -23±2%; celiprolol 10^-4 mol/L, -27±2%; nebivolol 10^-5 mol/L, -35±3%; NO: bopindolol 10^-6 mol/L, +33±2; celiprolol 10^-4 mol/L, +41±2; nebivolol 10^-5 mol/L, +45±5 fmol · min^-1 · g kidney^-1, mean±SEM). Metergoline (10^-6 mol/L), a 5-hydroxytryptamine (5-HT)_1/2 antagonist, or NAN-190 (10^-6 mol/L), a 5-HT_1A antagonist, almost completely abolished the vasorelaxation and NO release caused by bopindolol, celiprolol, and nebivolol. However, neither propranolol nor bisoprolol decreased RPP. Celiprolol and nebivolol caused vasodilation in the rat thoracic aorta, and it was markedly reduced by endothelial denudation, N-nitro-L-arginine methyl ester (10^-4 mol/L), or NAN-190 (10^-6 mol/L). In deoxycorticosterone acetate-salt hypertensive rats, 4-week administration of celiprolol (50 mg · kg^-1 · d^-1 IV) restored the responses regarding RPP and NO release to acetylcholine. These results suggest that several ß-blockers exert their vasodilatory action through the 5-HT_1A receptor/NO pathway and that treatment with these ß-blockers may protect against endothelial injury in hypertension.

Key Words: nitric oxide • kidney • receptors, adrenergic, beta • 5-hydroxytryptamine

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