Shepherd A M, Irvine N A
J Cardiovasc Pharmacol. 1986 May-Jun;8(3):527-33. doi: 10.1097/00005344-198605000-00014.
The hemodynamic and sympathoadrenal effects of serial incremental doses of a mixed veno-arteriolar dilator (intravenous sodium nitroprusside 0.0125-0.50 micrograms/kg/min) and a pure arteriolar dilator (bolus injections of hydralazine, 0.05-0.3 mg/kg) were compared in 18 subjects with uncomplicated essential hypertension. Blood pressure was reduced to the same extent over approximately the same time with both drugs. Sodium nitroprusside produced significant reduction in cardiac output (9%) and stroke volume (16%) despite an 11% increase in heart rate. Total peripheral resistance did not change. In contrast, hydralazine produced a significant (39%) reduction in peripheral resistance with a compensatory increase in heart rate (19%), stroke volume (20%), and cardiac output (42%). The catecholamine responses to the drugs differed both quantitatively and qualitatively. Administration of both drugs was associated with gradual increases in plasma norepinephrine, but the levels were consistently 40% higher with sodium nitroprusside for the same fall in blood pressure. No consistent change in plasma epinephrine was found with sodium nitroprusside, whereas with hydralazine, the concentration increased gradually after the blood pressure had been reduced by 9 mm Hg. This threshold was independent of the starting blood pressure. These differences in catecholamine response could reflect different patterns of regional sympathetic activation by the low pressure mechanoreceptors (sodium nitroprusside) and by the arterial baroreceptors (hydralazine). Neither drug has an ideal hemodynamic profile, particularly in subjects with cardiac disease, but a balanced combination of the two may produce a favorable hemodynamic profile and optimal hypotensive effect, minimizing the need for large doses of sympathetic inhibitors.
在18例无并发症的原发性高血压患者中,比较了连续递增剂量的混合性静脉 - 小动脉扩张剂(静脉注射硝普钠0.0125 - 0.50微克/千克/分钟)和单纯小动脉扩张剂(单次注射肼屈嗪,0.05 - 0.3毫克/千克)的血流动力学和交感肾上腺效应。两种药物在大致相同的时间内使血压降低到相同程度。硝普钠尽管心率增加了11%,但心输出量显著降低(9%),每搏输出量显著降低(16%)。总外周阻力未改变。相比之下,肼屈嗪使外周阻力显著降低(39%),同时心率代偿性增加(19%),每搏输出量增加(20%),心输出量增加(42%)。药物引起的儿茶酚胺反应在数量和质量上都有所不同。两种药物给药后血浆去甲肾上腺素均逐渐升高,但在血压下降相同幅度时,硝普钠组的血浆去甲肾上腺素水平始终高出40%。硝普钠给药后血浆肾上腺素未发现一致变化,而肼屈嗪给药后,血压降低9毫米汞柱后血浆肾上腺素浓度逐渐升高。该阈值与起始血压无关。儿茶酚胺反应的这些差异可能反映了低压机械感受器(硝普钠)和动脉压力感受器(肼屈嗪)对局部交感神经激活的不同模式。两种药物都没有理想的血流动力学特征,尤其是在患有心脏病的患者中,但两者的平衡组合可能会产生有利的血流动力学特征和最佳降压效果,从而最大限度地减少对大剂量交感神经抑制剂的需求。