Nebivolol induces NO-mediated relaxations of rat small mesenteric but not of large elastic arteries.

Abstract

Nebivolol is a newer beta1-selective adrenergic receptor antagonist, which unlike classic beta-blockers, lowers systemic vascular resistance by direct vasodilator effects possibly involving NO. This study was designed to determine the effects of nebivolol on small arteries, which contribute to the most part of systemic vascular resistance. Mesenteric arteries, isolated from 9-week-old Wistar-Kyoto (WKY) rats, were studied under perfused and pressurized conditions using a video dimension analyzer. Aortic rings from the same animals were suspended in organ chambers, and isometric tension was measured. Experiments were performed during contraction to prostaglandin F2alpha. In small arteries, nebivolol (10(-9) to 3 x 10(-5) M) induced concentration-dependent relaxations (maximum, 55 +/- 8%). The relaxations were less pronounced as compared with those to acetylcholine (maximum, 99 +/- 2%; p < 0.05), but were significantly greater than those to atenolol (maximum, 2 +/- 0%; p < 0.05). Nebivolol-induced responses were markedly reduced by the NO-synthase inhibitor N(omega)-nitro-L-arginine methylester (L-NAME; 10(-4) M; maximum, 11 +/- 2%; p < 0.05). This inhibition could be entirely reversed by pretreatment with L-arginine (10(-3) M; maximum, 46 +/- 7%), a precursor of NO. In contrast to mesenteric arteries, nebivolol did not affect vascular tension of precontracted aortas. These findings indicate that nebivolol induces NO-mediated relaxations in small arteries but not large elastic vessels and therefore, independent of its antihypertensive action, might be effective in protecting the microcirculation in various cardiovascular disease states.