Disparate effects of carvedilol versus metoprolol treatment of stroke-prone spontaneously hypertensive rats on endothelial function of resistance arteries

In human hypertension, blockade of beta-adrenoceptors does not improve resi stance artery structure or endothelial dysfunction. We tested in hypertensi ve rats the hypothesis that carvedilol, a beta-blocker with antioxidant pro perties, would improve endothelial dysfunction. whereas the beta(1)-selecti ve blocker, metoprolol, would not. Twenty-week-old SHRSP were treated orall y for 10 weeks with carvedilol (50 mg/kg day) or metoprolol (100 mg/kg/day) , with or without hydralazine (25 mg/kg/day), the latter because neither be ta-blocker was a very effective blood pressure-lowering agent in this model . Mesenteric arteries (lumen, <300 mu m) were studied on a pressurized myog raph. After 10 weeks, untreated SHRSP had a systolic blood pressure (mm Hg) of 239 +/- 3 that was unaffected by carvedilol or metoprolol treatment but decreased (p < 0.05) by hydralazine (187 +/- 4), carvedilol + hydralazine (221 + 3), and metoprolol + hydralazine (197 +/- 3). Carvedilol alone im pr oved endothelium-dependent relaxation of resistance arteries, as elicited b y the lowest concentration of acetylcholine studied (10(-7) M), whereas met oprolol had no effect. Hydralazine improved endothelial function as elicite d by acetylcholine at a dose of 10(-6) M. also found under cotreatment with carvedilol but attenuated by cotreatment with metoprolol. Carvedilol or me toprolol alone had no significant effect on endothelium-independent relaxat ion produced by a nitric oxide donor (sodium nitroprusside). However, vesse ls from rats treated with carvedilol + hydralazine exhibited significantly greater relaxation than those from rats treated with metoprolol + hydralazi ne. These data suggest that carvedilol may have favorable effects on hypert ension-related endothelial dysfunction not observed with metoprolol. Neithe r drug corrected small artery structure in SHRSP.