CARVEDILOL, A NEW BETA-ADRENOCEPTOR BLOCKER ANTIHYPERTENSIVE DRUG, PROTECTS AGAINST FREE-RADICAL-INDUCED ENDOTHELIAL DYSFUNCTION

We tested the ability of carvedilol, an antihypertensive beta-adrenoreceptor antagonist with antioxidant properties, to protect rat aorta rings from free-radical-induced endothelial cell (EC) dysfunction. Rings were exposed to the superoxide generator pyrogallol. Vascular function of intact rings was assessed by observing acetylcholine (ACh)-induced vasorelaxation following submaximal contraction by U-46619. Function of rings denuded of ECs was assessed by observing S-nitroso-N-acetylpenicillamine (SNAP)-induced vasorelaxation following submaximal contraction by U-46619. Carvedilol exerted a significant protective effect against pyrogallol-induced vasoconstriction (17.1 +/- 4.8 vs. 31.9 +/- 5.4% for vehicle, p < 0.05). Carvedilol also demonstrated significant protection against pyrogallol-induced endothelium dysfunction, enhancing vasorelaxation to 1,000 nmol/l ACh (73 +/- 3.9 vs. 48 +/- 3.0% vehicle, p < 0.01). These protective effects were not seen with propanolol, a pure beta-receptor antagonist. Carvedilol mixed with pyrogallol and SNAP preserved SNAP-induced vasorelaxation in rings denuded of ECs (80.4 +/- 5.3 vs. 63.7 +/- 4.8% control, p < 0.05). Carvedilol appears to protect vascular function by scavenging free radicals and enhancing the effects of NO.