Nakamura Y, Parent R, Lavallée M
Department of Physiology, Faculty of Medicine, University of Montreal Canada.
Circulation. 1991 Jul;84(1):300-12. doi: 10.1161/01.cir.84.1.300.
Previous studies in anesthetized animals indicated that substance P is a coronary and peripheral vasodilator. However, coronary vasodilation was only transient perhaps because of tachyphylaxis. In the present study, the steady-state effects of intravenous substance P on systemic and coronary beds were investigated in conscious, instrumented dogs.
With intact autonomic reflexes, 5 ng/kg/min i.v. substance P resulted in increases (p less than 0.01) in cardiac output by 22 +/- 5%, in decreases (p less than 0.01) in mean arterial pressure by 9 +/- 2%, and in total peripheral resistance by 23 +/- 4% 7-9 minutes after the beginning of substance P infusion. Heart rate increased (p less than 0.01) by 35 +/- 7% and left ventricular dP/dt (p less than 0.05) by 13 +/- 4%. In this situation, coronary blood flow decreased (p less than 0.01) by 19 +/- 4% and coronary vascular resistance increased (p less than 0.05) by 13 +/- 5%. Myocardial oxygen delivery was reduced (p less than 0.05) by 13 +/- 5% and the arteriovenous oxygen difference widened (p less than 0.01). After ganglionic blockade, increases in cardiac output, heart rate, and left ventricular dP/dt with substance P administration were abolished, but total peripheral resistance and mean arterial pressure decreased (p less than 0.01) by 12 +/- 3% respectively. Under these conditions, coronary blood flow decreased (p less than 0.01) by 37 +/- 5% and coronary vascular resistance increased (p less than 0.01) by 47 +/- 8%, which were more (p less than 0.01) than control responses. In this situation, myocardial oxygen delivery was reduced (p less than 0.01) by 37 +/- 4% and the arteriovenous oxygen difference widened (p less than 0.01). Intracoronary infusion of substance P (0.4 ng/kg/min) resulted in significant and sustained decreases in coronary blood flow, which were similar before and after ganglionic blockade.
Thus, in conscious dogs, systemic vasodilation is the prevailing effect of substance P, but paradoxically, this peptide simultaneously elicits coronary vasoconstriction.
先前对麻醉动物的研究表明，P物质是一种冠状动脉和外周血管扩张剂。然而，冠状动脉扩张可能只是短暂的，这可能是由于快速耐受性。在本研究中，在清醒的、植入仪器的犬身上研究了静脉注射P物质对全身和冠状动脉床的稳态影响。
在自主反射完整的情况下，静脉注射5 ng/kg/min的P物质，在开始输注P物质7 - 9分钟后，心输出量增加（p < 0.01）22±5%，平均动脉压降低（p < 0.01）9±2%，总外周阻力降低（p < 0.01）23±4%。心率增加（p < 0.01）35±7%，左心室dp/dt增加（p < 0.05）13±4%。在这种情况下，冠状动脉血流量减少（p < 0.01）19±4%，冠状动脉血管阻力增加（p < 0.05）13±5%。心肌氧输送减少（p < 0.05）13±5%，动静脉氧差增大（p < 0.01）。神经节阻断后，给予P物质时心输出量、心率和左心室dp/dt的增加被消除，但总外周阻力和平均动脉压分别降低（p < 0.01）12±3%。在这些条件下，冠状动脉血流量减少（p < 0.01）37±5%，冠状动脉血管阻力增加（p < 0.01）47±8%，比对照反应更明显（p < 0.01）。在这种情况下，心肌氧输送减少（p < 0.01）37±4%，动静脉氧差增大（p < 0.01）。冠状动脉内输注P物质（0.4 ng/kg/min）导致冠状动脉血流量显著且持续减少，在神经节阻断前后相似。
因此，在清醒犬中，全身血管扩张是P物质的主要作用，但矛盾的是，这种肽同时引起冠状动脉收缩。
