Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells

1 Carvedilol, an adrenoceptor blocker with antioxidant activity, was studie d for its ability to interact with NO in a cell-free condition and in an en dothelial cell line (ECV304). 2 In a cell-free system, carvedilol attenuated NO-dependent reduction of ca rboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide induced by a NO donor, 1-hydroxy-2-oxo-3-(aminopropyl)3-isopropyl-1-triazene (NOC5), whi ch was determined by electron paramagnetic resonance (EPR) spectrometry. Th e EPR study also showed that nitrosylhaemoglobin formation in rat red blood cells by the addition of NO-saturated solution was attenuated by prior inc ubation with 0.1-10 mu M carvedilol. 3 NO-induced fluorescence in 4,5-diaminofluorescein-2 diacethyl (DAF-2DA)-l oaded ECV304 cells was attenuated by carvedilol but not by labetalol. The I C50 of carvedilol for NOC5 of sodium nitroprusside-induced fluorescence of DAF-2DA in ECV304 cells was 1.0 x 10(-7) M, which was similar to the report ed IC50 of carvedilol for the antioxidant effect. 4 Cell toxicity induced by a NO donor determined by the number of viable ce lls after 24 h treatment with 2-2'(hydroxynitrosohydrazino)bis-ethanamine w as significantly attenuated by pretreatment with 1 mu M carvedilol. 5 Both free and cell-associated carvedilol quenched NO. Because NO mediates both physiological and pathophysiological processes, NO quenching by the d rug may have diverse clinical implications depending upon specific function s of local NO in tissues where carvedilol is distributed.