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Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart

Abstract : The cardiac effects of the NO donors sodium nitroprusside (SNP), S-nitroso-N-acetyl-penicillamine (SNAP) and 3-morpholino-sydnonimine (SIN-1) were studied in frog fibres to evaluate the contribution of cyclic GMP-dependent mechanisms. SNP and SNAP (0·1-100 μM) reduced the force of contraction in a concentration-dependent manner in atrial and ventricular fibres. This effect was associated with a reduction in the time to peak (TTP) and the time for half-relaxation of contraction (T½). SIN-1 (100 μM) also reduced the force of contraction in two-thirds of the atrial fibres. However, it exerted a positive inotropic effect in the remaining atrial fibres, as well as in most ventricular fibres. The guanylyl cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 μM) antagonized the negative inotropic effects of SIN-1 (50 μM) and SNAP (25 μM) but had no effect on the positive inotropic response to SIN-1 (100 μM). In the presence of SIN-1, superoxide dismutase (SOD, 50-200 U ml−1) either potentiated the negative inotropic effect or turned the positive inotropic effect of the drug into a negative effect. SOD had no effects when applied alone or in the presence of SNAP. 6-Anilino-5,8-quinolinedione (LY 83583, 3-30 μM), a superoxide anion generator also known as a cyclic GMP-lowering agent, exerted a positive inotropic effect, which was antagonized by SOD (200-370 U ml−1) but not by ODQ (10 μM). 7 We conclude that SNP, SNAP and SIN-1 exert cyclic GMP-dependent negative inotropic effects, which are attributed to the generation of NO. In addition, SIN-1 and LY 83583 exert cyclic GMP-independent positive inotropic effects, which require the generation of superoxide anion.
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Jean‐michel Chesnais, Rodolphe Fischmeister, Pierre‐françois Méry. Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart. The Journal of Physiology, Wiley, 1999, 518 (2), pp.449-461. ⟨10.1111/j.1469-7793.1999.0449p.x⟩. ⟨hal-03612184⟩



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