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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H728    most recent 00022.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhong, B. Articles by Wang, D. H. Search for Related Content PubMed PubMed Citation Articles by Zhong, B. Articles by Wang, D. H.

N-oleoyldopamine, a novel endogenous capsaicin-like lipid, protects the heart against ischemia-reperfusion injury via activation of TRPV1

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 January 2008 ; accepted in final form 10 June 2008

N-oleoyldopamine (OLDA), a bioactive lipid originally found in the mammalian brain, is an endovanilloid that selectively activates the transient receptor potential vanilloid type 1 (TRPV1) channel. This study tests the hypothesis that OLDA protects the heart against ischemia and reperfusion (I/R) injury via activation of the TRPV1 in wild-type (WT) but not in gene-targeted TRPV1-null mutant (TRPV1^–/–) mice. Hearts of WT or TRPV1^–/– mice were Langendorffly perfused with OLDA (2 x 10^–9 M) in the presence or absence of CGRP8–37 (1 x 10^–6 M), a selective calcitonin gene-related peptide (CGRP) receptor antagonist; RP-67580 (1 x 10^–6 M), a selective neurokinin-1 receptor antagonist; chelerythrine (5 x 10^–6 M), a selective protein kinase C (PKC) antagonist; or tetrabutylammonium (TBA, 5 x 10^–4 M), a nonselective K⁺ channel antagonist, followed by 35 min of global ischemia and 40 min of reperfusion (I/R). Left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), coronary flow (CF), and left ventricular peak positive dP/dt (+dP/dt) were evaluated after I/R. OLDA improved recovery of cardiac function after I/R in WT but not TRPV1^–/– hearts by increasing LVDP, CF, and +dP/dt and by decreasing LVEDP. CGRP8–37, RP-67580, chelerythrine, or TBA abolished the protective effect of OLDA in WT hearts. Radioimmunoassay showed that the release of substance P (SP) and CGRP after OLDA treatment was higher in WT than in TRPV1^–/– hearts, which was blocked by chelerythrine or TBA. Thus OLDA exerts a cardiac protective effect during I/R injury in WT hearts via CGRP and SP release, which is abolished by PKC or K⁺ channel antagonists. The protective effect of OLDA is void in TRPV1^–/– hearts, supporting the notion that TRPV1 mediates OLDA-induced protection against cardiac I/R injury.

N-oleoyldopamine; transient receptor potential vanilloid 1; ischemia-reperfusion; substance P; calcitonin gene-related peptide; protein kinase C antagonist; potassium ion channel antagonist; gene knockout