Drieu la Rochelle C, Berdeaux A, Richard V, Giudicelli J F
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
J Cardiovasc Pharmacol. 1991 Dec;18(6):904-10. doi: 10.1097/00005344-199112000-00018.
The effects of YM-16151 (1 mg/kg, i.v.), a combined beta 1-adrenoceptor blocking and calcium antagonist drug, on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs at rest and during treadmill exercise. These effects were compared to those in the same animals of nicardipine (0.1 mg/kg, i.v.), atenolol (1 mg/kg, i.v.) and their combination (at the same doses). Circumflex artery diameter (CxAD) and coronary blood flow increased and coronary vascular resistance (CVR) decreased during control exercise under saline. YM-16151 and the nicardipine-atenolol combination similarly dilated large and small coronary arteries at rest, but dilation of large conductance vessels was abolished during exercise, while CVR decreased further. Both YM-16151 and the nicardipine-atenolol combination only slightly increased the rate-pressure product at rest, but strongly opposed its exercise-induced rise. Nicardipine maximally increased CxAD, decreased CVR, and enhanced the rate-pressure product at rest and during exercise. Conversely, atenolol decreased CxAD and the rate-pressure product and increased CVR at rest, but large coronary arteries remained constricted during exercise despite the concomitant dilation of small resistance vessels. Thus, in the coronary vascular bed of conscious dogs, YM-16151 really behaves as a hybrid drug, combining beta 1-adrenoceptor blocking and calcium antagonist properties, both at rest and during exercise. As a result, YM-16151 increases oxygen supply at rest and decreases oxygen demand during exercise. Finally, this study emphasizes the major role of beta 1-adrenoceptors in the mediation of exercise-induced dilation of large coronary arteries.
在慢性植入仪器的清醒犬处于静息状态和跑步机运动期间，研究了YM - 16151（1毫克/千克，静脉注射），一种兼具β1肾上腺素能受体阻断和钙拮抗剂作用的药物，对大（回旋支动脉）、小冠状动脉以及全身血流动力学的影响。将这些影响与相同动物使用尼卡地平（0.1毫克/千克，静脉注射）、阿替洛尔（1毫克/千克，静脉注射）及其组合（相同剂量）时的影响进行比较。在生理盐水对照的运动期间，回旋支动脉直径（CxAD）和冠状动脉血流量增加，冠状动脉血管阻力（CVR）降低。YM - 16151和尼卡地平 - 阿替洛尔组合在静息时同样能扩张大、小冠状动脉，但在运动期间大传导血管的扩张作用消失，而CVR进一步降低。YM - 16151和尼卡地平 - 阿替洛尔组合在静息时仅轻微增加速率 - 压力乘积，但强烈对抗其运动诱导的升高。尼卡地平在静息和运动期间最大程度地增加CxAD，降低CVR，并提高速率 - 压力乘积。相反，阿替洛尔在静息时降低CxAD和速率 - 压力乘积，并增加CVR，但尽管小阻力血管同时扩张，大冠状动脉在运动期间仍保持收缩。因此，在清醒犬的冠状动脉血管床中，YM - 16151在静息和运动时确实表现为一种兼具β1肾上腺素能受体阻断和钙拮抗剂特性的混合药物。结果，YM - 16151在静息时增加氧供应，在运动时减少氧需求。最后，本研究强调了β1肾上腺素能受体在运动诱导的大冠状动脉扩张介导中的主要作用。
