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首页> 外文期刊>Life sciences >Negative inotropic effects of angiotensin II, endothelin-1 and phenylephrine in indo-1 loaded adult mouse ventricular myocytes.
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Negative inotropic effects of angiotensin II, endothelin-1 and phenylephrine in indo-1 loaded adult mouse ventricular myocytes.

机译：血管紧张素II，内皮素-1和去氧肾上腺素对indo-1加载的成年小鼠心室肌细胞的负性肌力作用。

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摘要

Angiotensin II (Ang II). endothelin-1 (ET-1) and phenylephrine are receptor agonists that share the signal transduction acting through acceleration of phosphoinositide hydrolysis in the heart. Because the regulation of myocardial contractility induced by these receptor agonists shows a wide range of species-dependent variation among experimental animals, we carried out experiments to elucidate the mechanism of contractile regulation induced by these agents in mice which are employed currently more as transgenic models. Effects of Ang II, ET-1 and phenylephrine on cell shortening and Ca2+ transients were investigated in single ventricular myocytes loaded with indo-1/AM. Ang II (10(-8), 10(-7) M), ET-1 (10(-10), 10(-9) M) and phenylephrine (10(-6), 10(-5) M in the presence of the beta-adrenoceptor antagonist timolol) decreased the cell shortening [Ang II: 58.4+/-9.03 (n = 8), 50.3+/-11.90% (n = 6); ET-1: 48.4+/-8.27, 31.2+/-6.45% (n = 5); phenylephrine: 45.7+/-11.60, 28.7+/-5.89% (n = 5)]. By contrast, the amplitude of Ca2+ transients was not significantly influenced by these agonists. The selective protein kinase C inhibitor chelerythrine at 10(-6) M significantly inhibited the decrease in cell shortening induced by these receptor agonists. These results indicate that Ang II, ET-1 and phenylephrine elicit a negative inotropic effect with insignificant alteration of Ca2+ transients, which may be mainly mediated by activation of protein kinase C in mouse ventricular cardiomyocytes.
机译：血管紧张素II（Ang II）。内皮素-1（ET-1）和去氧肾上腺素是受体激动剂，它们通过加速心脏中磷酸肌醇水解而共享信号转导。由于这些受体激动剂引起的心肌收缩力调节在实验动物中表现出广泛的物种依赖性变化，因此我们进行了实验以阐明这些试剂在小鼠中诱导的收缩调节机制，目前这些小鼠更多地被用作转基因模型。在载有indo-1 / AM的单个心室肌细胞中研究了Ang II，ET-1和去氧肾上腺素对细胞缩短和Ca2 +瞬变的影响。 Ang II（10（-8），10（-7）M），ET-1（10（-10），10（-9）M）和去氧肾上腺素（10（-6），10（-5）M in β-肾上腺素受体拮抗剂替莫洛尔的存在降低了细胞缩短[Ang II：58.4 +/- 9.03（n = 8），50.3 +/- 11.90％（n = 6）; ET-1：48.4 +/- 8.27，31.2 +/- 6.45％（n = 5）;苯肾上腺素：45.7 +/- 11.60，28.7 +/- 5.89％（n = 5）]。相反，这些激动剂对Ca 2+瞬变的幅度没有显着影响。选择性蛋白激酶C抑制剂白屈菜红碱在10（-6）M处显着抑制了这些受体激动剂诱导的细胞缩短的减少。这些结果表明，Ang II，ET-1和去氧肾上腺素引起负性肌力作用，而Ca2 +瞬变变化不明显，这可能主要是由小鼠心室心肌细胞中蛋白激酶C的激活介导的。

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