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 resistance artery structure or endothelial dysfunction. We tested in hypertensive rats the hypothesis that carvedilol, a beta-blocker with antioxidant properties, would improve endothelial dysfunction, whereas the beta1-selective blocker, metoprolol, would not. Twenty-week-old SHRSP were treated orally 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 beta-blocker was a very effective blood pressure-lowering agent in this model. Mesenteric arteries (lumen, <300 microm) were studied on a pressurized myograph. 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 improved endothelium-dependent relaxation of resistance arteries, as elicited by the lowest concentration of acetylcholine studied (10(-7) M), whereas metoprolol had no effect. Hydralazine improved endothelial function as elicited by acetylcholine at a dose of 10(-6) M, also found under cotreatment with carvedilol but attenuated by cotreatment with metoprolol. Carvedilol or metoprolol alone had no significant effect on endothelium-independent relaxation produced by a nitric oxide donor (sodium nitroprusside). However, vessels from rats treated with carvedilol + hydralazine exhibited significantly greater relaxation than those from rats treated with metoprolol + hydralazine. These data suggest that carvedilol may have favorable effects on hypertension-related endothelial dysfunction not observed with metoprolol. Neither drug corrected small artery structure in SHRSP.
Intengan
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MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada.
Schiffrin
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D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D008790:Metoprolol / Q000627:therapeutic use*; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol