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Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1791-8. Epub 2007 Jun 22.

TRPV1 gene knockout impairs preconditioning protection against myocardial injury in isolated perfused hearts in mice.

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  • 1Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.

Abstract

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 CGRP(8-37), 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(-/-). CGRP(8-37) 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.

PMID:
17586621
[PubMed - indexed for MEDLINE]
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