AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 294: H1291-H1297, 2008. First published January 11, 2008; doi:10.1152/ajpheart.00749.2007
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Deletion of the mouse {alpha}-calcitonin gene-related peptide gene increases the vulnerability of the heart to ischemia-reperfusion injury

Ruiping Huang,1 Amrita Karve,1 Ibrahim Shah,1 Mark C. Bowers,2 Donald J. DiPette,2 Scott C. Supowit,2 and George S. Abela1

1Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; and 2Scott & White Health System and the Department of Medicine, College of Medicine, Texas A&M University System Health Science Center, Temple, Texas

Submitted 28 June 2007 ; accepted in final form 7 January 2008

Calcitonin gene-related peptide (CGRP), a potent vasodilator released from capsaicin-sensitive C-fiber and A{delta}-fiber sensory nerves, has been suggested to play a beneficial role in myocardial ischemia-reperfusion (I/R) injury. Because most previous studies showing a cardioprotective role of CGRP employed pharmacological experiments, the purpose of this study was to utilize a genetic approach by using mice with a targeted deletion of the {alpha}-CGRP gene to determine whether this neuropeptide had a modulatory function on the severity of I/R injury. To accomplish this goal, isolated, perfused hearts from {alpha}-CGRP knockout (KO) and wild-type (WT) mice were subjected to 30 min of ischemia followed by 5, 15, and 30 min of reperfusion. Cardiac functional parameters, including coronary flow rates, left ventricular developed pressure, maximum rates of pressure development, and left ventricular end-diastolic pressure, were measured before and after I/R injury, as were levels of creatine kinase, to assess myocardial damage, and malonaldehyde, to assess oxidative stress. Following I/R injury, cardiac performance was significantly reduced in the hearts from the {alpha}-CGRP KO mice compared with their WT counterparts. The marked reduction in myocardial function in the {alpha}-CGRP KO hearts compared with WT hearts after I/R injury was associated with a significant elevation in creatine kinase release into the perfusates and malonaldehyde production in the cardiac tissue. Therefore, these data indicate that, in this in vitro setting, deletion of {alpha}-CGRP makes the heart more vulnerable to I/R injury, possibly due, at least in part, to increased oxidative stress.

genetically modified mice; cardiac; isolated perfused heart preparations; sensory nervous system


Address for reprint requests and other correspondence: S. C. Supowit, Dept. of Cell and Developmental Biology and Anatomy, School of Medicine, Univ. of South Carolina, 6439 Garners Ferry Rd., Bldg. 3, Columbia, SC 29209 (e-mail: ssupowit{at}gw.med.sc.edu)






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