Drexler H, Flaim S F, Fields R H, Zelis R
J Pharmacol Exp Ther. 1985 Feb;232(2):376-81.
This study examined the effects of the dihydropyridine derivative nisoldipine (1.6 micrograms/kg/min) on hemodynamics and regional blood flow (radioactive microspheres, 15 +/- 5 microns) in conscious rats at rest and during treadmill exercises (35 feet/min, 5 min). Nisoldipine significantly reduced systemic vascular resistance (-38%) and mean arterial pressure (-17%) and increased heart rate (P less than .05). Skeletal muscle blood flow was increased and vascular resistances in the skeletal muscle, in renal and coronary arteries and in part of the gut circulations were significantly reduced (all P less than .05). Left ventricular end-diastolic pressure was unchanged by the drug both at rest and during exercise. At exercise, nisoldipine significantly increased skeletal muscle blood flow in four of eight skeletal muscle regions investigated; however, the increase in total skeletal muscle flow was less pronounced compared to the changes at rest. The vasodilator effect of nisoldipine in the renal and splanchnic circulations was markedly attenuated by the exercise-induced vasoconstriction in these circulatory beds. We conclude that nisoldipine is a potent vasodilator of skeletal muscle and coronary and renal arteries. It appears to possess highly selective effects on vascular smooth muscle as compared to its direct cardiac effects.
本研究检测了二氢吡啶衍生物尼索地平(1.6微克/千克/分钟)对清醒大鼠静息及跑步机运动(35英尺/分钟,5分钟)时血流动力学和局部血流(放射性微球,15±5微米)的影响。尼索地平显著降低全身血管阻力(-38%)和平均动脉压(-17%),并增加心率(P<0.05)。骨骼肌血流量增加,骨骼肌、肾动脉、冠状动脉及部分肠道循环的血管阻力显著降低(均P<0.05)。药物对静息及运动时的左心室舒张末期压力均无影响。运动时,尼索地平显著增加了所研究的八个骨骼肌区域中四个区域的骨骼肌血流量;然而,与静息时的变化相比,总骨骼肌血流量的增加不太明显。运动诱导的这些循环床血管收缩显著减弱了尼索地平在肾循环和内脏循环中的血管舒张作用。我们得出结论,尼索地平是骨骼肌、冠状动脉和肾动脉的强效血管舒张剂。与其直接的心脏作用相比,它似乎对血管平滑肌具有高度选择性作用。