The relaxant properties in guinea pig airways of S-nitrosothiols

作者: J. Loscalzo , J. S. Stamler , J. M. Drazen , R. Brown , J. A. Osborne

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摘要: Several cellular constituents of the lung have capacity to synthesize a factor capable relaxing smooth muscle which has physicochemical properties nitric oxide (NO). In other systems, it been shown that NO may be stabilized in plasma and milieu by reduced thiol form an S-nitrosothiol (RS-NO). These compounds half-lives are significantly greater than NO, also retain vasorelaxant activity is mediated activating guanylate cyclase raising cyclic GMP levels. The effects RS-NO their potential mechanism action on airways, however, not previously investigated. this study, we examined relaxant several biological synthetic guinea pig trachea. Our data reveal generally potent airway relaxants with at least partial effect through stimulation GMP. Relaxations were attenuated inhibitor methylene blue (P less .05), RS-NO-induced increases demonstrated .0005). IC50 values for S-nitroso-glutathione, S-nitroso-cysteine, S-nitroso-homocysteine, S-nitroso-N-acetylcysteine, S-nitroso-penicillamine S-nitroso-captopril 0.99 +/- 0.09, 3.2 0.2, 2.1 0.3, 0.8, 1.8 0.8 20 0.7 microM (mean S.E.M.), respectively. system isoproterenol 0.016 theophylline 74 microM, making these derivatives pharmacological physiological relevance.

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