Gasic S, Eichler H G, Korn A
Int J Clin Pharmacol Ther Toxicol. 1987 Jul;25(7):382-8.
Aim of the study was to investigate whether nifedipine interacts with alpha1-mediated splanchnic and systemic vasoconstriction in man. The effects of nifedipine on basal and phenylephrine (PE)-induced hemodynamic changes were studied in 6 normotensive men, using the hepatic venous catheter technique (indocyanine-green) and the thermodilution method. After a baseline period, nifedipine was given by constant infusion (0.5 microgram/kg/min) and, after equilibration, PE was infused at a constant rate in a dose sequence of 1, 2, 3, and 4 micrograms/kg/min, until the systolic blood pressure was raised by 30 mmHg. Control trials without nifedipine (saline) were also performed in each subject. At basal conditions nifedipine decreased systemic blood pressure and total systemic vascular resistance (TSVR) as well as total pulmonary vascular resistance (TPVR), and increased cardiac output (CO). PE provoked a dose-dependent increase in systemic blood pressure, TSVR and TPVR, and decreased CO. These PE-effects were clearly attenuated by nifedipine. In the splanchnic vascular bed nifedipine increased estimated splanchnic blood flow (ESBF) and decreased splanchnic vascular resistance (SVR) at basal conditions. The PE-induced decrease in ESBF and increase in SVR were inhibited or attenuated (depending on PE-dosage) by nifedipine. We conclude that nifedipine counteracts alpha1-adrenoceptor mediated systemic and splanchnic vasoconstriction and therefore, might also be useful in the treatment of intestinal vasospasm.
本研究的目的是调查硝苯地平是否与人的α1介导的内脏和全身血管收缩相互作用。使用肝静脉导管技术(吲哚菁绿)和热稀释法,在6名血压正常的男性中研究了硝苯地平对基础状态和去氧肾上腺素(PE)诱导的血流动力学变化的影响。在基线期后,以恒定输注速率(0.5微克/千克/分钟)给予硝苯地平,平衡后,以1、2、3和4微克/千克/分钟的剂量序列以恒定速率输注PE,直至收缩压升高30 mmHg。每个受试者也进行了无硝苯地平(生理盐水)的对照试验。在基础状态下,硝苯地平降低了全身血压、总全身血管阻力(TSVR)以及总肺血管阻力(TPVR),并增加了心输出量(CO)。PE引起全身血压、TSVR和TPVR的剂量依赖性增加,并降低了CO。硝苯地平明显减弱了这些PE效应。在内脏血管床,硝苯地平在基础状态下增加了估计的内脏血流量(ESBF)并降低了内脏血管阻力(SVR)。硝苯地平抑制或减弱了(取决于PE剂量)PE诱导的ESBF降低和SVR增加。我们得出结论,硝苯地平可对抗α1肾上腺素能受体介导的全身和内脏血管收缩,因此,也可能对治疗肠道血管痉挛有用。