Khayyal M, Gross F, Kreye V A
J Pharmacol Exp Ther. 1981 Feb;216(2):390-4.
In contrast to other large arteries commonly used in organ bath studies, the rabbit renal artery is highly sensitive to the vasodilator action of hydralazine. Helical strips contracted by 10(-7) M norepinephrine started to relax at a threshold concentration of 3.9 x 10(-8) M hydralazine (IC10). The IC50 was 1.4 x 10(-7) M, and at 3 x 10(-6) M hydralazine, the preparations had relaxed almost completely. The development of relaxation was slow, lasting up to 1 hr. Dose-response curves to norepinephrine in the presence of hydralazine were shifted to the right in parallel fashion at an only slight reduction of the maximum response. Contractions of rabbit renal artery strips induced by 45 mM, KCl, or by 10(-7) M norepinephrine superimposed on the KCl-induced tone, were almost unresponsive to hydralazine. Similarly, prolonged incubation of the arterial strips with 10(-5) M ouabain abolished the response to hydralazine probably as a result of a ouabain-induced depolarization. Neither indomethacin, an inhibitor of tissue prostaglandin synthesis, nor sulpiride, an antagonist to dopamine, interfered significantly with the vasodilator action of hydralazine. This suggests that the relaxant effect of hydralazine is not mediated by locally formed prostaglandins and that it is not dopaminergic in nature. The present findings indicate that hydralazine is a potent direct vasodilator with a predominant action on pharmacomechanical coupling but little effect on electromechanical coupling.
与器官浴研究中常用的其他大动脉不同，兔肾动脉对肼屈嗪的血管舒张作用高度敏感。由10(-7) M去甲肾上腺素收缩的螺旋条在肼屈嗪阈值浓度3.9 x 10(-8) M（IC10）时开始松弛。IC50为1.4 x 10(-7) M，在3 x 10(-6) M肼屈嗪时，制剂几乎完全松弛。松弛的发展缓慢，持续长达1小时。在存在肼屈嗪的情况下，去甲肾上腺素的剂量-反应曲线以平行方式向右移动，最大反应仅略有降低。由45 mM氯化钾或叠加在氯化钾诱导的张力上的10(-7) M去甲肾上腺素诱导的兔肾动脉条收缩对肼屈嗪几乎无反应。同样，用10(-5) M哇巴因长时间孵育动脉条可能由于哇巴因诱导的去极化而消除了对肼屈嗪的反应。组织前列腺素合成抑制剂吲哚美辛和多巴胺拮抗剂舒必利均未显著干扰肼屈嗪的血管舒张作用。这表明肼屈嗪的松弛作用不是由局部形成的前列腺素介导的，并且其本质上不是多巴胺能的。目前的研究结果表明，肼屈嗪是一种有效的直接血管舒张剂，对药物-机械偶联具有主要作用，但对电-机械偶联影响很小。
