Effects of in vivo nebivolol treatment on NO-signalling (A) and endothelial function (B)
J. Vasc. Biol. 42, Sup:2 (2005) p38
| P111 | Nebivolol inhibits angiotensin II-induced aortic and cardiac superoxide formation and expression and activity of NADPH oxidase subunits p67phox and rac-1. |
| M.Oelze, A.Daiber, Ph.Wenzel, U.Hink, H.Mollnau, A.Mülsch, T.Münzel | |
| Johannes Gutenberg University Hospital, Mainz, DE. | |
|
Nebivolol is a β1-adrenergic receptor antagonist with vasodilator and antioxidant properties. Since NADPH oxidases are important superoxide (O2-) sources we studied the effect of nebivolol on endothelial function and NADPH oxidase in angiotensin II (Ang-II) induced hypertension. In male Wistar rats 7d Ang-II infusion (1 mg/kg/d) caused endothelial dysfunction, indicated by a decreased vasodilator potency of acetylcholine in isolated aortic rings, a 2.5 fold increase in O2- formation in aortic vessels and in NADPH oxidase activity in heart membrane fractions, as detected by lucigenin- (5μM) derived chemiluminescence (LDCL). Staining of aortic sections with the fluorescent dye dihydroethidine showed O2- formation throughout the vessel wall. Expression of NADPH oxidase subunits was increased in aorta (p67phox 248±42%, rac-1 168±7% of control) and heart membranes (p67phox 259±17%, rac-1 169±26%). In addition, an enhanced membrane-association of p67phox and rac-1 was detected. Co-treatment with nebivolol (10 mg/kg/d) normalized endothelial function and O2- formation and prevented upregulation and membrane-association of p67phox and rac-1. Furthermore, in vitro treatment with nebivolol but not atenolol or metoprolol induced a dissociation of p67phox and rac-1 as well as a reduction in NADPH oxidase activity assessed in heart membranes from Ang-II infused animals. Thus, inhibitory effects of nebivolol on vascular NADPH oxidase activity may explain at least in part its beneficial effect on endothelial function in oxidative stress-related cardiovascular diseases such as heart failure and atherosclerosis. |
| Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher. |