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pubmed:abstractText |
Carvedilol (0.25-25 microM), an antihypertensive drug is shown here to reduce endothelin-1 (ET-1) production in cultured human umbilical cord endothelial cells. Two of its metabolites, M14 and M21 (2.5-25 microM) also suppressed ET-1 production, less potently, however, than carvedilol. Carvedilol is a multiple-acting compound with non-selective beta-adrenoceptor and selective alpha 1-adrenoceptor blocking activity, calcium channel blocking and anti-oxidant activity. To study whether these activities were related to suppressed ET-1 production, endothelial cells were treated with a beta 1-blocker, metoprolol (1-10 microM), a non-selective beta-blocker, propanolol (1-10 microM), an alpha 1-blocker, prazosin (1-10 microM), a calcium channel antagonist, nicardipine (1-10 microM), or with the antioxidative compounds probucol (1-100 microM) and ascorbic acid (1-100 microM). None of these compounds modified ET-1 production. The inhibitory effects of carvedilol, M14 or M21 on ET-1 production were not reversed by N Nitro-L-arginine methyl ester (L-NAME) (1.9 mM), or by indomethacin (1.5 microM), suggesting that mechanisms other than the stimulation of nitric oxide or prostacyclin production were involved.
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