Sekiguchi N, Kanatsuka H, Sato K, Wang Y, Akai K, Komaru T, Takishima T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Circulation. 1994 Jan;89(1):366-74. doi: 10.1161/01.cir.89.1.366.
Calcitonin gene-related peptide (CGRP) is a potent dilator of epicardial conduit vessels and is released during myocardial ischemia in humans. However, the effect of CGRP on coronary arterial microvessels is still unclear, and it is unknown if CGRP modulates the tone of coronary arterial microvessels during acute myocardial ischemia.
Epimyocardial microvessels were observed through a microscope equipped with a floating objective system in anesthetized open-chest dogs. Heart rate and aortic pressure were maintained at control levels. Flow velocity of the left anterior descending coronary artery (LAD) was measured with a suction-cup Doppler probe. When CGRP was cumulatively infused into the LAD (0.05, 0.5, 5.0, and 50 pmol/kg per minute) or superfused (0.03, 0.3, 3.0, and 30 nmol/L) over the left ventricular surface, arterial control microvessels > 100 microns in diameter dilated dose dependently at dosages of 0.5 to 50 pmol/kg per minute (infused) or 0.3 to 30 nmol/L (superfused), but those < 100 microns dilated only at the highest dose, and those > 100 microns had greater dilation in both groups. Only the highest dose of CGRP (infused) significantly increased coronary flow. The superfusion of CGRP(8-37) (CGRP receptor antagonist, 300 nmol/L) did not affect the control diameters of coronary arterial microvessels but completely abolished CGRP-induced vasodilation at the same doses (infused and superfused). However, 300 nmol/L of CGRP(8-37) did not affect the response of coronary arterial microvessels to the LAD occlusion in any size.
CGRP preferentially dilates the coronary arterial microvessels > 100 microns in diameter but has only a small effect on those < 100 microns. Endogenous CGRP does not modulate the tone of coronary arterial microvessels during acute myocardial ischemia in beating canine hearts.
降钙素基因相关肽（CGRP）是一种强效的心外膜传导血管扩张剂，在人类心肌缺血时会释放。然而，CGRP对冠状动脉微血管的作用仍不清楚，并且在急性心肌缺血期间CGRP是否调节冠状动脉微血管的张力也未知。
在麻醉开胸犬中，通过配备浮动物镜系统的显微镜观察心外膜微血管。心率和主动脉压维持在对照水平。用吸盘式多普勒探头测量左前降支冠状动脉（LAD）的血流速度。当将CGRP以累积方式注入LAD（每分钟0.05、0.5、5.0和50 pmol/kg）或在左心室表面进行超灌注（0.03、0.3、3.0和30 nmol/L）时，直径>100微米的动脉对照微血管在以每分钟0.5至50 pmol/kg（注入）或0.3至30 nmol/L（超灌注）的剂量下呈剂量依赖性扩张，但直径<100微米的微血管仅在最高剂量时扩张，且在两组中直径>100微米的微血管扩张更明显。仅最高剂量的CGRP（注入）显著增加冠状动脉血流量。CGRP（8-37）（CGRP受体拮抗剂，300 nmol/L）的超灌注不影响冠状动脉微血管的对照直径，但在相同剂量（注入和超灌注）下完全消除了CGRP诱导的血管舒张。然而，300 nmol/L的CGRP（8-37）对任何大小的冠状动脉微血管对LAD闭塞的反应均无影响。
CGRP优先扩张直径>100微米的冠状动脉微血管，但对直径<100微米的微血管影响较小。在跳动的犬心脏急性心肌缺血期间，内源性CGRP不调节冠状动脉微血管的张力。
