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

• Published in: American journal of physiology. Heart and circulatory physiology 2008-08, Vol.295 (2), p.H728-H735
• Main Authors: Zhong, Beihua, Wang, Donna H
• Format: Article
• Language: English
• Subjects: Animals; Antagonist drugs; Benzophenanthridines - pharmacology; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide - pharmacology; Coronary Circulation; Dopamine - analogs & derivatives; Dopamine - metabolism; Heart; Isoindoles - pharmacology; Kinases; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia - complications; Myocardial Ischemia - metabolism; Myocardial Ischemia - physiopathology; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Neurokinin-1 Receptor Antagonists; Peptide Fragments - pharmacology; Peptides; Potassium Channel Blockers - pharmacology; Potassium Channels - metabolism; Protection; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Protein Kinase Inhibitors - pharmacology; Quaternary Ammonium Compounds - pharmacology; Radioimmunoassay; Receptors, Calcitonin Gene-Related Peptide - antagonists & inhibitors; Receptors, Calcitonin Gene-Related Peptide - metabolism; Receptors, Neurokinin-1 - metabolism; Rodents; Studies; Substance P - metabolism; TRPV Cation Channels - deficiency; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Ventricular Function, Left; Ventricular Pressure
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00022.2008

1 Department of Medicine, 2 Neuroscience Program, and 3 Cell and Molecular Biology Program, Michigan State University, East Lansing, Michigan; and 4 Department 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/d t (+dP/d t ) 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/d t 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 Address for reprint requests and other correspondence: D. H. Wang, Dept. of Medicine, B316 Clinical Center, Michigan State Univ., East Lansing, MI 48824 (e-mail: donna.wan