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 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.


RESULTS
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.


CONCLUSIONS
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.
Sekiguchi
N
N
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Kanatsuka
H
H
Sato
K
K
Wang
Y
Y
Akai
K
K
Komaru
T
T
Takishima
T
T
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide