Imai N, Kashiki M, Woolf P D, Liang C S
Department of Medicine, University of Rochester Medical Center, New York 14642.
Am J Physiol. 1994 Sep;267(3 Pt 2):H912-7. doi: 10.1152/ajpheart.1994.267.3.H912.
We have shown previously that right heart failure (RHF) in dogs is associated with activated endogenous opiate systems, and that administration of the opioid receptor antagonist, naloxone, increases arterial pressure, cardiac contractile function and organ blood flows. To study whether the cardiovascular effects of naloxone are mediated via the mu- or delta-opioid receptors, we administered ICI-154,129, a delta-receptor antagonist, and naloxonazine, a mu-receptor antagonist, to 10 conscious dogs with RHF on 2 separate days. Like naloxone, ICI-154,129 increased mean aortic pressure, cardiac output, peak positive first derivative of left ventricular pressure, and blood flows to the myocardium, kidneys, splanchnic beds, and skeletal muscle. These changes were associated with increases in plasma epinephrine and norepinephrine. In contrast, naloxonazine had no effects on systemic hemodynamics, regional blood flow distribution, and plasma catecholamines in RHF. These findings suggest that the increased endogenous opioids during heart failure act on the delta-opioid receptors to decrease myocardial mechanical performance and alter regional blood flow distribution. Opioid receptor-blocking agents may exert beneficial cardiovascular effects in heart failure.
我们之前已经表明，犬类右心衰竭（RHF）与内源性阿片系统激活有关，并且给予阿片受体拮抗剂纳洛酮可提高动脉压、心脏收缩功能和器官血流量。为了研究纳洛酮的心血管效应是否通过μ或δ阿片受体介导，我们在2个不同的日子给10只患有RHF的清醒犬分别给予δ受体拮抗剂ICI - 154,129和μ受体拮抗剂纳洛嗪。与纳洛酮一样，ICI - 154,129可提高平均主动脉压、心输出量、左心室压力的正向一阶导数峰值以及流向心肌、肾脏、内脏床和骨骼肌的血流量。这些变化与血浆肾上腺素和去甲肾上腺素升高有关。相比之下，纳洛嗪对RHF犬的全身血流动力学、局部血流分布和血浆儿茶酚胺没有影响。这些发现表明，心力衰竭期间内源性阿片类物质增加，作用于δ阿片受体，降低心肌机械性能并改变局部血流分布。阿片受体阻断剂可能对心力衰竭发挥有益的心血管作用。
