Effects of vasodilatory beta-adrenoceptor antagonists on endothelium-derived nitric oxide release in rat kidney

The mechanisms for the vascular actions of vasodilatory beta-blockers remai n undetermined. For some kinds of beta-blockers, the involvement of nitric oxide (NO) has been suggested. We studied the effects of vasodilatory beta- 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, -3 5+/-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) antagon ist, or NAN-190 (10(-6) mol/L), a 5-HT1A antagonist, almost completely abol ished the vasorelaxation and NO release caused by bopindolol, celiprolol, a nd nebivolol. However, neither propranolol nor bisoprolol decreased RPP. Ce liprolol and nebivolol caused vasodilation in the rat thoracic aorta, and i t was markedly reduced by endothelial denudation, N-omega-nitro-L-arginine methyl ester (10(-4) mol/L), or NAN-190 (10-6 mol/L). In deoxycorticosteron e acetate-salt hypertensive rats, 4-week administration of celiprolol (50 m g . kg(-1) . d(-1) IV) restored the responses regarding RPP and NO release to acetylcholine. These results suggest that several beta-blockers exert th eir vasodilatory action through the 5-HT1A receptor/NO pathway and that tre atment with these beta-blockers may protect against endothelial injury in h ypertension.