Lee J Y, Krueger A D, Walsh G M
Department of Biological Research, G.D. Searle and Co., Skokie, IL 60077.
J Hypertens. 1988 Dec;6(12):1017-22. doi: 10.1097/00004872-198812000-00010.
Verapamil (1 mg/kg, i.v.) and nifedipine (0.3 mg/kg, i.v.) were tested at equi-antihypertensive doses for systemic hemodynamic responses in conscious spontaneously hypertensive rats (SHR) using the Fick method. Systemic hemodynamic effects of these agents were also evaluated in areflexic, spinal cord-transected and vagotomized SHR using the electromagnetic flowmetry technique. Both verapamil and nifedipine lowered mean arterial pressure (MAP:verapamil = -24%; nifedipine = -28%) in conscious SHR by decreasing total peripheral resistance (TPR:verapamil = -48%; nifedipine = -59%) with a concomitant rise in cardiac output (CO: verapamil = 48%; nifedipine = 86%) and stroke volume (SV:verapamil = 54%; nifedipine = 65%), but verapamil prevented tachycardia, whereas nifedipine increased heart rate (HR:13%). Verapamil and nifedipine also altered systemic hemodynamics in the areflexic SHR; verapamil reduced MAP (-31%) by reducing CO (-18%) with associated bradycardia (-25% HR), whereas nifedipine also lowered MAP (-21%) by decreasing TPR (-18%) without changes in CO and HR. It is concluded that, firstly, the antihypertensive action of verapamil and nifedipine in conscious SHR is due to systemic vasodilation that is associated with reflexly increased CO; secondly, that verapamil has a direct negative chronotropic effect, but nifedipine appears to be devoid of such an effect, and finally that the ability of verapamil to decrease TPR may depend upon resting sympathetic tone.
维拉帕米(1毫克/千克,静脉注射)和硝苯地平(0.3毫克/千克,静脉注射)以等降压剂量进行测试,采用菲克法研究清醒自发性高血压大鼠(SHR)的全身血流动力学反应。还使用电磁血流测量技术在去反射、脊髓横断和迷走神经切断的SHR中评估了这些药物的全身血流动力学效应。维拉帕米和硝苯地平均可降低清醒SHR的平均动脉压(MAP:维拉帕米=-24%;硝苯地平=-28%),方法是降低总外周阻力(TPR:维拉帕米=-48%;硝苯地平=-59%),同时心输出量(CO:维拉帕米=48%;硝苯地平=86%)和每搏输出量(SV:维拉帕米=54%;硝苯地平=65%)增加,但维拉帕米可预防心动过速,而硝苯地平会使心率增加(HR:13%)。维拉帕米和硝苯地平也改变了去反射SHR的全身血流动力学;维拉帕米通过降低CO(-18%)并伴有心动过缓(-25%HR)来降低MAP(-31%),而硝苯地平也通过降低TPR(-18%)来降低MAP(-21%),CO和HR无变化。得出的结论是,首先,维拉帕米和硝苯地平在清醒SHR中的降压作用是由于全身血管舒张,这与反射性增加的CO有关;其次,维拉帕米具有直接的负性变时作用,但硝苯地平似乎没有这种作用,最后,维拉帕米降低TPR的能力可能取决于静息交感神经张力。