Campos-Toimil M, Orallo F, Gil-Longo J, Verde I, Loza I, Fernández-Alzueta A
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, La Coruña, Spain.
Eur J Pharmacol. 1994 Jan 4;251(1):83-90. doi: 10.1016/0014-2999(94)90446-4.
We have studied several effects of hydralazine in the bisected rat vas deferens. Hydralazine produced a shift to the left of the concentration-response curve for noradrenaline, with potentiation of the maximal response in both portions of the vas deferens. In contrast it caused a shift to the right of the concentration-response curve for noradrenaline in preparations pretreated with cocaine (inhibitor of catecholamine neuronal uptake), and of the curve for methoxamine and for CaCl2 (in depolarizing medium with K+ 55 mM), in all cases with depression of the maximal response. Hydralazine enhanced the contractions induced by noradrenaline in Ca(2+)-free medium, except in the presence of cocaine. It had no effect on [3H]noradrenaline neuronal uptake into noradrenergic neurons of the vas deferens, nor did it affect basal or K(+)-induced 45Ca2+ uptake. These results suggest that hydralazine potentiates the contractions elicited by noradrenaline by a mechanism other than blockade of the neuronal uptake of this catecholamine. Our results also suggest that the inhibition by hydralazine of the contractions elicited by Ca2+ (in Ca(2+)-free depolarizing high-K+ 55 mM solution) and by methoxamine is not due to an action on voltage-dependent Ca2+ channels, but may reflect an intracellular site of action.
我们研究了肼屈嗪对大鼠离体输精管的多种作用。肼屈嗪使去甲肾上腺素的浓度-反应曲线左移，且使输精管两部分的最大反应增强。相比之下，在预先用可卡因（儿茶酚胺神经元摄取抑制剂）处理的标本中，肼屈嗪使去甲肾上腺素的浓度-反应曲线右移；在含55 mM钾的去极化培养基中，它使甲氧明和氯化钙的曲线右移，所有这些情况下最大反应均降低。在无钙培养基中，除存在可卡因的情况外，肼屈嗪增强了去甲肾上腺素诱导的收缩。它对输精管去甲肾上腺素能神经元摄取[3H]去甲肾上腺素没有影响，也不影响基础或钾诱导的45Ca2+摄取。这些结果表明，肼屈嗪增强去甲肾上腺素引发的收缩，其机制不是通过阻断该儿茶酚胺的神经元摄取。我们的结果还表明，肼屈嗪对钙（在无钙去极化高钾55 mM溶液中）和甲氧明引发的收缩的抑制作用，并非由于对电压依赖性钙通道的作用，而可能反映了细胞内作用位点。
