NIFEDIPINE POTENTIATES CARDIOPULMONARY BAROREFLEX CONTROL OF SYMPATHETIC-NERVE ACTIVITY IN HEALTHY HUMANS - DIRECT EVIDENCE FROM MICRONEUROGRAPHIC STUDIES
NIFEDIPINE POTENTIATES CARDIOPULMONARY BAROREFLEX CONTROL OF SYMPATHETIC-NERVE ACTIVITY IN HEALTHY HUMANS - DIRECT EVIDENCE FROM MICRONEUROGRAPHIC STUDIES
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DOI：
10.1161/01.cir.80.2.285
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发表时间：
1989-08-01
期刊：
影响因子：
37.8
通讯作者：
HAYES, DW
中科院分区：
文献类型：
--
作者：
FERGUSON, DW;HAYES, DW
硝苯地平增强体内动物模型的压力反射机制。我们实验室以前的研究表明，硝苯地平增强了正常人对压力感受性反射的心率和血管阻力的控制。为了进一步明确硝苯地平自主神经作用的神经效应机制，我们在给药前后、在下体负压(-10 mm Hg，LBNP-10)下选择性卸载心肺压力感受器时和在冷加压试验中，直接测量了节后交感神经对肌肉的活动(MSNA，显微神经学检查)。23名正常受试者(年龄23。+-。1年；平均+-在硝普钠滴注(0.37±-)的过程中，分别在对照组和硝苯地平(10 mg s.l，10例受试者)给药20分钟后进行扫描电子显微镜观察。0.03微克/公斤/分静脉注射，8名受试者)，或舌下注射安慰剂20分钟后(5名受试者)。我们测量了全身动脉压、中心静脉压、心率和MSNA。硝苯地平和硝普钠对静息心率和MSNA有类似的增加，中心静脉压有类似的下降，而安慰剂对静息血流动力学没有影响。在LBNP-10期间，三个治疗组之间的血流动力学变化没有显著差异。然而，在LBNP-10期间，MSNA的增加百分比从24.+-显著增加。硝苯地平治疗前增加9%至56。+-。硝苯地平治疗后增加7%(p<；0.05)。与硝苯地平治疗前相比，LBNP-10治疗后中心静脉压的下降几乎相同。因此，硝苯地平使心肺压力感受性反射交感神经敏感度(下体负压期间中心静脉压每毫米汞柱下降总MSNA的变化)从26.5±-。10.7个单位/毫米汞至74.9.+-19.0单位/毫米汞柱(p<；0.01)。相反，给予血流动力学相似剂量的硝普钠导致MSNA对LBNP10-的反应减弱。在LBNP-10期间，MSNA增加了57.+-。硝普钠前有12%，但只有14.%+-。硝普钠组4%(p<；0.01)。硝普钠(45.1±-)对心肺压力感受性反射的交感敏感性无明显影响。12.4个单位/毫米汞，之前为33.1+-。硝普钠时20.8个单位/毫米汞，p=NS)。安慰剂对LBNP-10的反应没有影响。硝苯地平不增加MSNA对冷加压试验的反应。为了评价心肺压力感受器卸载后交感神经反应的线性，在另外三个受试者中应用了分级下体负压(0、-5、-10和-15 mm Hg)：硝苯地平(10 mg s.l)前后。在所有三个受试者中，下体负压递增使MSNA呈线性增加，硝苯地平增强了这种反应的心肺压力感受性反射交感敏感性：从36.6到97.4，从40.9到138.8，从13.4U/mm Hg增加到37.1U/mm Hg。因此，硝苯地平选择性地增强正常人对卸载心肺压力感受器的交感神经效应器反应。这种效应似乎不是由于非特异性血管扩张剂的影响，也不反映反射反应性的普遍增加。我们推测，硝苯地平增敏人类的心肺压力感受器，与在动物身上观察到的对压力感受器的影响相似。
NIfedipine augments baroreflex mechanisms in in vivo animal models. Previous studies in our laboratory demonstrate that nifedipine potentiates baroreflex control of heart rate and vascular resistance in normal human subjects. To further define the neuroeffector mechanism of the autonomic effects of nifedipine, we directly measured postganglionic sympathetic nerve activity to muscle (MSNA, microneurography), before and after drug administration, during selective unloading of cardiopulmonary baroreceptors with lower body negative pressure (-10 mm Hg, LBNP-10), and during the cold pressor test. Twenty-three normal subjects (age, 23 .+-. 1 years; mean .+-. SEM) were studied in the control state and 20 minutes after administration of either nifedipine (10 mg s.l., 10 subjects) during nitroprusside infusion (0.37 .+-. 0.03 .mu.g/kg/min i.v., eight subjects), or 20 minutes after sublingual administration of placebo (five subjects). We measured systemic arterial pressure, central venous pressure, heart rate, and MSNA. Nifedipine and nitroprusside produced similar increases in resting heart rate and MSNA and similar decreases in central venous pressure, whereas placebo had no effect on resting hemodynamics. During LBNP-10, hemodynamic changes were not significantly different among the three treatment groups. However, the percentage increase in MSNA during LBNP-10 was significantly augmented from a 24 .+-. 9% increase before nifedipine to a 56 .+-. 7% increase after nifedipine (p < 0.05). Decreases in central venous pressure with LBNP-10 were nearly identical before compared with after nifedipine. Thus, nifedipine increased the cardiopulmonary baroreflex sympathetic senitivity (change in total MSNA per mm Hg decrease in central venous pressure during LBNP-10) from 26.5 .+-. 10.7 units/mm Hg to 74.9 .+-. 19.0 units/mm Hg (p < 0.01). In contrast, administration of hemodynamically similar doses of nitroprusside resulted in an attenuation of MSNA responses to LBNP10-. During LBNP-10, MSNA increased 57 .+-. 12% before nitroprusside but only 14 .+-. 4% during nitroprusside (p < 0.01). The cardiopulmonary baroreflex sympathetic sensitivity was not significantly altered by nitroprusside (45.1 .+-. 12.4 units/mm Hg before compared with 33.1 .+-. 20.8 units/mm Hg during nitroprusside, p = NS). Placebo had no effect on the responses to LBNP-10. Nifedipine did not augment MSNA responses to the cold pressor test. To evaluate the linearity of sympathetic responses to cardiopulmonary baroreceptor unloading, graded LBNP (0, -5, -10, and -15 mm Hg) was applied in three additional subjects: before and after nifedipine (10 mg s.l.) Graded LBNP produced a linear increase in MSNA and nifedipine potentiated the cardiopulmonary baroreflex sympathetic sensitivity of this response in all three subjects: from 36.6 to 97.4, from 40.9 to 138.8, and from 13.4 to 37.1 units/mm Hg. Thus, nifedipine selectively potentiates sympathetic neuroeffector responses to unloading of cardiopulmonary baroreceptors in normal humans. This effect does not appear to be due to a nonspecific vasodilator affect nor does it reflect a generalized increase in reflex responsiveness. We speculate that nifedipine sensitizes cardiopulmonary baroreceptors in humans, similar to the effect observed on baroreceptors in animals.