Nakamura Y, Parent R, Lavallee M
Department of Physiology, Faculty of Medicine, University of Montreal, Quebec, Canada.
Am J Physiol. 1990 Feb;258(2 Pt 2):H565-73. doi: 10.1152/ajpheart.1990.258.2.H565.
The effects of substance P (SP) on epicardial coronary diameter (CD) and coronary blood flow (CBF) were examined in conscious dogs. SP (5.0 ng/kg) induced transient increases (P less than 0.01) in CBF by 139 +/- 19% from 26.5 +/- 1.5 ml/min followed by sustained decreases (P less than 0.01) averaging 22 +/- 2% when mean arterial pressure had returned to preinjection base line. CD increased (P less than 0.01) by 6.7 +/- 1.4% from 3.47 +/- 0.35 mm. After ganglionic blockade with hexamethonium (35 mg/kg), the transient increases (P less than 0.01) in CBF (95 +/- 10% from 28.6 +/- 1.9 ml/min) were smaller (P less than 0.05), but the late decreases (P less than 0.01) in CBF averaged 23 +/- 3%, similar to responses before ganglionic blockade. Increases (P less than 0.01) in CD (4.1 +/- 0.7% from 3.49 +/- 0.35 mm) were smaller (P less than 0.05) than before ganglionic blockade. During steady-state effects of SP (5.0 ng.kg-1.min-1) under ganglionic blockade, CBF fell (P less than 0.01) by 39 +/- 3% from 26.4 +/- 2.3 ml/min, but CD increased (P less than 0.01) by 6.6 +/- 1.6% from 3.45 +/- 0.40 mm. Additional experiments indicated that coronary sinus blood oxygen content fell and myocardial arteriovenous O2 difference increased during steady-state effects of SP under ganglionic blockade. Cyclooxygenase inhibition did not alter coronary responses to SP. Endothelial denudation abolished increases in CD after SP. Therefore, under steady-state conditions and in the absence of autonomic reflexes, SP is a potent endothelium-dependent dilator of conductance coronary vessels but paradoxically a constrictor of resistance coronary vessels.
在清醒犬中研究了P物质（SP）对心外膜冠状动脉直径（CD）和冠状动脉血流量（CBF）的影响。SP（5.0 ng/kg）使CBF短暂增加（P<0.01），从26.5±1.5 ml/min增加139±19%，随后当平均动脉压恢复到注射前基线时持续下降（P<0.01），平均下降22±2%。CD从3.47±0.35 mm增加（P<0.01）6.7±1.4%。用六甲铵（35 mg/kg）进行神经节阻断后，CBF的短暂增加（P<0.01）（从28.6±1.9 ml/min增加95±10%）较小（P<0.05），但CBF的后期下降（P<0.01）平均为23±3%，与神经节阻断前的反应相似。CD的增加（P<0.01）（从3.49±0.35 mm增加4.1±0.7%）比神经节阻断前小（P<0.05）。在神经节阻断下SP（5.0 ng·kg-1·min-1）的稳态作用期间，CBF从26.4±2.3 ml/min下降（P<0.01）39±3%，但CD从3.45±0.40 mm增加（P<0.01）6.6±1.6%。额外的实验表明，在神经节阻断下SP的稳态作用期间，冠状窦血氧含量下降，心肌动静脉氧差增加。环氧化酶抑制并未改变冠状动脉对SP的反应。内皮剥脱消除了SP后CD的增加。因此，在稳态条件下且无自主反射时，SP是传导性冠状动脉血管的一种强效内皮依赖性扩张剂，但矛盾的是，它是阻力性冠状动脉血管的一种收缩剂。
