Nievelstein H M, Van Essen H, Tijssen C M, Smits J F, Struyker Boudier H A
Eur J Pharmacol. 1985 Jul 17;113(2):187-98. doi: 10.1016/0014-2999(85)90735-6.
In the present study we investigated systemic and regional hemodynamic effects of the calcium entry blockers nifedipine, verapamil and PY 108-068 in conscious SHR. For systemic hemodynamic studies the animals were instrumented with an electromagnetic flowprobe on the ascending aorta, whereas for regional hemodynamic studies miniaturized Doppler flowprobes were implanted on the superior mesenteric and left renal artery and on the abdominal aorta. All three drugs caused a dose-dependent fall in mean arterial pressure and total peripheral resistance. Nifedipine and PY 108-068 increased cardiac output and heart rate, whereas verapamil only did so at high doses. Administration of each calcium entry blocker caused a dose-dependent fall in skeletal muscle vascular resistance, with renal and mesenteric resistance remaining virtually unchanged. A similar effect was observed after the administration of nifedipine to normotensive WKY rats. Surgical elimination of sino-aortic baroreflexes caused a 10 fold increase in antihypertensive potency of the three drugs in SHR. Moreover, dilatation in these animals was uniform in all beds studied. The results indicate that the three calcium entry blockers used are essentially non-selective vasodilators but that baroreflex mechanisms prevent vasodilatation in the renal and mesenteric beds in intact animals.
在本研究中，我们调查了钙通道阻滞剂硝苯地平、维拉帕米和PY 108 - 068对清醒自发性高血压大鼠（SHR）全身和局部血流动力学的影响。对于全身血流动力学研究，动物在升主动脉上安装电磁血流探头；而对于局部血流动力学研究，将小型化多普勒血流探头植入肠系膜上动脉、左肾动脉和腹主动脉。所有三种药物均导致平均动脉压和总外周阻力呈剂量依赖性下降。硝苯地平和PY 108 - 068增加心输出量和心率，而维拉帕米仅在高剂量时才会如此。每种钙通道阻滞剂的给药均导致骨骼肌血管阻力呈剂量依赖性下降，肾和肠系膜阻力基本保持不变。给正常血压的WKY大鼠服用硝苯地平后也观察到类似效果。手术消除窦主动脉压力反射导致这三种药物对SHR的降压效力增加10倍。此外，在这些动物中，所有研究部位的血管扩张都是均匀的。结果表明，所使用的三种钙通道阻滞剂本质上是非选择性血管扩张剂，但压力反射机制可防止完整动物肾和肠系膜血管床的血管扩张。
