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Am J Physiol Heart Circ Physiol 293: H1791-H1798, 2007. First published June 22, 2007; doi:10.1152/ajpheart.00169.2007
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TRPV1 gene knockout impairs preconditioning protection against myocardial injury in isolated perfused hearts in mice

Beihua Zhong1,4 and Donna H. Wang1,2,3

1Department of Medicine, 2Neuroscience Program, and 3Cell and Molecular Biology Program, Michigan State University, East Lansing, Michigan; and 4Department of Pharmacology, Guangzhou Medical College, Guangzhou, China

Submitted 9 February 2007 ; accepted in final form 18 June 2007

Although the transient receptor potential vanilloid type 1 (TRPV1)-containing afferent nerve fibers are widely distributed in the heart, the relationship between TRPV1 function and cardiac ischemic preconditioning (PC) has not been well defined. Using TRPV1 knockout mice (TRPV1–/–), we studied the role of TRPV1 in PC-induced myocardial protection. Hearts of gene-targeted TRPV1-null mutant (TRPV1–/–) or wild-type (WT) mice were Langendorffly perfused in the presence or absence of CGRP8-37, a selective calcitonin gene-related peptide (CGRP) receptor antagonist; or RP-67580, a selective neurokinin-1 receptor antagonist when hearts were subjected to three 5-min periods of ischemia PC followed by 30 min of global ischemia and 40 min of reperfusion (I/R). PC before I/R decreased left ventricular (LV) end-diastolic pressure and increased LV developed pressure, coronary flow (CF), peak-positive maximum rate of rise of LV pressure in WT mice (PC-WT) compared with PC-TRPV1–/–, TRPV1–/–, or WT hearts (P < 0.05), and PC also decreased LV end-diastolic pressure in PC-TRPV1–/– compared with TRPV1–/–. CGRP8-37 or RP-67580 abolished PC-induced protection in WT but not TRPV1–/– hearts (P < 0.05). Moreover, PC decreased lactate dehydrogenase release and infarct size in PC-WT compared with PC-TRPV1–/–, TRPV1–/–, or WT hearts, and it also lowered these parameters in PC-TRPV1–/– compared with TRPV1–/– hearts (P < 0.05). Radioimmunoassay showed that the release of substance P and CGRP after PC was higher in WT hearts than in TRPV1–/– hearts (P < 0.05), which was attenuated by capsazepine in WT but not TRPV1–/– hearts. Thus PC-induced protection of the heart was impaired in TRPV1–/– hearts, indicating that TRPV1 contributes to the beneficial effects of preconditioning against I/R injury through release substance P and CGRP.

transient receptor potential vanilloid type 1; ischemia-reperfusion; substance P; calcitonin gene-related peptide



Address for reprint requests and other correspondence: D. H. Wang, Dept. of Medicine, B316 Clinical Ctr., Michigan State Univ., East Lansing, MI 48824 (e-mail: donna.wang{at}ht.msu.edu)




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