EFFECT OF CALCITONIN-GENE-RELATED PEPTIDE ON CORONARY MICROVESSELS AND ITS ROLE IN ACUTE MYOCARDIAL-ISCHEMIA

Background Calcitonin gene-related peptide (CGRP) is a potent dilator of epicardial conduit vessels and is released during myocardial ischem ia in humans. However, the effect of CGRP on coronary arterial microve ssels is still unclear, and it is unknown if CGRP modulates the tone o f coronary arterial microvessels during acute myocardial ischemia. Met hods and Results Epimyocardial microvessels were observed through a mi croscope equipped with a floating objective system in anesthetized ope n-chest dogs. Heart rate and aortic pressure were maintained at contro l levels. Flow velocity of the left anterior descending coronary arter y (LAD) was measured with a suction-cup Doppler probe. When CGRP was c umulatively infused into the LAD (0.05, 0.5, 5.0, and 50 pmol/kg per m inute) or superfused (0.03, 0.3, 3.0, and 30 nmol/L) over the left ven tricular surface, arterial control microvessels >100 mu m in diameter dilated dose dependently at dosages of 0.5 to 50 pmol/kg per minute (i nfused) or 0.3 to 30 nmol/L (superfused), but those <100 mu m dilated only at the highest dose, and those >100 mu m had greater dilation in both groups. Only the highest dose of CGRP (infused) significantly inc reased coronary flow. The superfusion of CGRP(8-37) (CGRP receptor ant agonist, 300 nmol/L) did not affect the control diameters of coronary arterial microvessels but completely abolished CGRP-induced vasodilati on at the same doses (infused and superfused). However, 300 nmol/L of CGRP(8-37) did not affect the response of coronary arterial microvesse ls to the LAD occlusion in any size. Conclusions CGRP preferentially d ilates the coronary arterial microvessels >100 mu m in diameter but ha s only a small effect on those <100 mu m. Endogenous CGRP does not mod ulate the tone of coronary arterial microvessels during acute myocardi al ischemia in beating canine hearts.