Humphrey S J, Zins G R
J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):979-88.
Microsphere estimates of whole body hemodynamics and tissue blood flow were made in conscious and pentobarbital-anesthetized dogs treated orally with the peripheral vasodilator minoxidil. Under both circumstances, 1.0-30 mg/kg minoxidil significantly reduced mean arterial pressure 21-41% and total peripheral resistance 52-75% 4 h after administration. Dose-dependent increases in heart rate and cardiac output were evident under conscious conditions, with both parameters approximately doubling at 1.0 mg/kg. The near maximal vasodilation achieved with this dose of minoxidil was due to diminished vascular resistance in all major tissue beds. The enhanced cardiac output was associated with significant 50-87% increases in blood flow to the skin, skeletal muscle, bone, stomach, large intestine, and pancreas. Far more dramatic six- to 10-fold increases in regional myocardial blood flow were seen at this dose, which appeared to be only partially dependent on increased cardiac work. Comparable blood flow patterns were seen with acute minoxidil at doses greater than 1.0 mg/kg, and with chronic minoxidil at 1.0 and 30 mg/kg/day. These experiments establish minoxidil's relative vasodilation in the major tissue beds of the dog which contributes to its hypotensive activity.
对口服外周血管扩张剂米诺地尔的清醒和戊巴比妥麻醉犬进行了全身血流动力学和组织血流的微球估计。在这两种情况下,给药4小时后,1.0 - 30mg/kg的米诺地尔显著降低平均动脉压21 - 41%,并使总外周阻力降低52 - 75%。在清醒状态下,心率和心输出量呈剂量依赖性增加,在1.0mg/kg时这两个参数均增加约一倍。该剂量米诺地尔实现的近乎最大程度的血管舒张是由于所有主要组织床的血管阻力降低。心输出量增加与皮肤、骨骼肌、骨骼、胃、大肠和胰腺的血流量显著增加50 - 87%有关。在该剂量下,局部心肌血流量出现了更为显著的6至10倍的增加,这似乎仅部分依赖于心脏作功增加。大于1.0mg/kg的急性米诺地尔以及1.0和30mg/kg/天的慢性米诺地尔呈现出类似的血流模式。这些实验确定了米诺地尔在犬主要组织床中的相对血管舒张作用,这有助于其降压活性。