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Abstract
The following experiments were conducted to determine whether, and the mechanisms
through which, endogenous peptides alter coronary artery blood flow. Ultrasonic transit
time probes were placed around the ascending aorta and left anterior descending coronary
artery in groups of anesthetized, open-chest dogs. A Millar pressure catheter monitored
left ventricular developed pressure. Intracoronary artery bolus injections of adenosine
(a purinergic receptor activator), pinacidil (a KATPchannel activator), calcitonin gene-related peptide (CGRP; which causes vascular smooth
muscle relaxation by intracellular increases in cyclic-AMP), and adrenomedullin (mechanism
unknown) each significantly (P< 0.05, Student'sttest) increased coronary blood flow in a dose-dependent fashion, without altering
systemic hemodynamic measurements. Intracoronary artery injection of U37883A (a KATPchannel antagonist) significantly (P< 0.05) blocked the coronary vasodilator responses to adenosine, adrenomedullin, and
pinacidil. Intracoronary xanthine amine congener (an adenosine receptor antagonist)
blocked only the responses to adenosine and adrenomedullin, not pinacidil. Intracoronary
CGRP8-37(CGRP receptor antagonist) blocked only the vasodilator response to CGRP. These data
suggest that the coronary vasodilator effect of adrenomedullin is initiated first
by activation of adenosine receptors, and subsequently through KATPchannels—not by activation of CGRP receptors. That there were no changes in left ventricular
developed pressure or in systemic hemodynamics after intracoronary artery infusions
of adrenomedullin indicates that this endogenous peptide may have clinical utility
in facilitating myocardial protection or preconditioning.
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References
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Article info
Footnotes
☆T. Devlin, Ed.
Identification
Copyright
© 1997 Academic Press. Published by Elsevier Inc. All rights reserved.
