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Effect of SIN-1 in rat ventricular myocytes: interference with beta-adrenergic stimulation.

机译:SIN-1在大鼠心室肌细胞中的作用:干扰β-肾上腺素能刺激。

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摘要

We have examined the effects of the nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on Ca(2+) transients, L-type Ca(2+) current (I(Ca,L)), and cGMP/cAMP content in electrically-stimulated rat ventricular myocytes in the absence and presence of the beta-adrenergic stimulation with isoproterenol. SIN-1 had no effect at low concentrations, but decreased the amplitude of electrically-induced Ca(2+) transients at higher concentrations. SIN-1 attenuated the increase in Ca(2+) transients induced by isoproterenol in a concentration-dependent manner. SIN-1 Also reduced the amplitude of caffeine-induced Ca(2+) transients, and the increase in I(Ca,L) induced by isoproterenol. These effects of SIN-1 were associated with an increased cGMP and a decreased cAMP content in ventricular myocytes in either the absence or presence of isoproterenol. These data suggest that the inhibitory effect of SIN-1 on basal and beta-adrenergic stimulated Ca2+ signal in ventricular myocytes could be due to the depression in the SR function and I(Ca,L), possibly mediated by a cGMP/cAMP-dependent mechanism. Taken together, the present study supports the idea that NO acts as an inhibitory modulator of the cardiac function during pathological conditions associated with an abnormal production of NO such as septic shock.
机译:我们已经检查了一氧化氮(NO)供体3-吗啉代亚砜(SIN-1)对Ca(2+)瞬变,L型Ca(2+)电流(I(Ca,L))的影响,以及在不存在和存在异丙肾上腺素刺激的情况下,电刺激的大鼠心室肌细胞中cGMP / cAMP的含量。 SIN-1在低浓度下没有作用,但在较高浓度下降低了电感应Ca(2+)瞬变的幅度。 SIN-1以浓度依赖的方式减弱了异丙肾上腺素诱导的Ca(2+)瞬变的增加。 SIN-1还减少了咖啡因诱导的Ca(2+)瞬变的幅度,以及由异丙肾上腺素诱导的I(Ca,L)的增加。在不存在或存在异丙肾上腺素的情况下,SIN-1的这些作用与cGMP升高和心室肌细胞cAMP含量降低有关。这些数据表明,SIN-1对基础和β-肾上腺素刺激的心室肌细胞Ca2 +信号的抑制作用可能是由于SR功能和I(Ca,L)降低所致,可能是由cGMP / cAMP依赖性介导的。机制。综上所述,本研究支持这样的想法,即在与败血症性休克等NO的异常产生有关的病理状态下,NO可以抑制心脏功能。

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