Hirsch A T, Dzau V J, Cutler S S, Levenson D J, Creager M A
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115.
J Cardiovasc Pharmacol. 1992 Feb;19(2):272-81. doi: 10.1097/00005344-199202000-00016.
Calcium channel antagonists, when used to treat hypertension, may modulate baroreflex function and vascular responsiveness to endogenous vasoconstrictors. We studied regional blood flow, cardiopulmonary baroreflex function, and pressor responses in nine hypertensive patients (mean age of 44 +/- 7 years), eight males and one female, treated with isradipine (ISR), a dihydropyridine calcium channel antagonist, in a placebo-controlled, crossover trial. Each patient underwent determination of blood pressure and forearm, splanchnic, and renal blood flows (by strain gauge plethysmography and indocyanine green and p-aminohippurate clearances, respectively) at baseline and during cardiopulmonary unloading by lower body negative pressure (LBNP) at -10 and -20 mm Hg. ISR decreased the mean arterial pressure from 105 +/- 2 to 93 +/- 2 mm Hg (p less than 0.01). ISR did not change supine forearm or splanchnic vascular resistances, but renal vascular resistance fell 30% during treatment (from 0.12 +/- 0.02 to 0.09 +/- 0.01 mm Hg min/ml, p less than 0.05). Cardiopulmonary baroreceptor unloading by LBNP elicited comparable effects on forearm, splanchnic, and renal vascular resistance before and during ISR treatment. Baroreceptor unloading during placebo did not change plasma NE or PRA; during ISR, LBNP elicited a progressive rise in these hormones. The pressor response to NE was potentiated during ISR treatment (p less than 0.05); in contrast, the pressor response to angiotensin II infusion was blunted by calcium blockade (p less than 0.05). The present study, therefore, demonstrates that calcium channel blockade with ISR preserves, and may even augment, cardiopulmonary baroreflex function. These physiologic responses may contribute to the relatively low incidence of symptomatic orthostatic hypotension observed during chronic treatment with this agent.
钙通道拮抗剂用于治疗高血压时，可能会调节压力反射功能以及血管对内源性血管收缩剂的反应性。在一项安慰剂对照的交叉试验中，我们研究了9例高血压患者（平均年龄44±7岁，8例男性，1例女性）在使用二氢吡啶类钙通道拮抗剂伊拉地平（ISR）治疗时的局部血流、心肺压力反射功能和升压反应。每位患者在基线时以及通过下体负压（LBNP）在-10和-20 mmHg进行心肺卸载期间，分别通过应变片体积描记法以及吲哚菁绿和对氨基马尿酸清除率测定血压、前臂血流、内脏血流和肾血流。ISR使平均动脉压从105±2 mmHg降至93±2 mmHg（p<0.01）。ISR未改变仰卧位时的前臂或内脏血管阻力，但治疗期间肾血管阻力下降了30%（从0.12±0.02 mmHg·min/ml降至0.09±0.01 mmHg·min/ml，p<0.05）。在ISR治疗前和治疗期间，通过LBNP进行心肺压力感受器卸载对前臂、内脏和肾血管阻力产生了类似的影响。安慰剂期间压力感受器卸载未改变血浆去甲肾上腺素（NE）或肾素活性（PRA）；在ISR治疗期间，LBNP使这些激素逐渐升高。在ISR治疗期间，对NE的升压反应增强（p<0.05）；相反，钙通道阻滞剂可减弱对血管紧张素II输注的升压反应（p<0.05）。因此，本研究表明，使用ISR进行钙通道阻滞可保留甚至增强心肺压力反射功能。这些生理反应可能有助于解释在使用该药物进行慢性治疗期间观察到的症状性直立性低血压发生率相对较低的现象。
