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

Abstract

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.

• Authors: Beihua Zhong, Donna H Wang
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 295 Issue 2 Pg. H728-35 (Aug 2008) ISSN: 0363-6135 [Print] United States
• PMID: 18567714 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Benzophenanthridines
• Calcitonin Gene-Related Peptide Receptor Antagonists
• Isoindoles
• Neurokinin-1 Receptor Antagonists
• Peptide Fragments
• Potassium Channel Blockers
• Potassium Channels
• Protein Kinase Inhibitors
• Quaternary Ammonium Compounds
• Receptors, Calcitonin Gene-Related Peptide
• Receptors, Neurokinin-1
• TRPV Cation Channels
• TRPV1 protein, mouse
• calcitonin gene-related peptide (8-37)
• 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
• Substance P
• tetrabutylammonium
• chelerythrine
• Protein Kinase C
• Calcitonin Gene-Related Peptide
• N-oleoyldopamine
• Dopamine

Topics

• Animals
• Benzophenanthridines (pharmacology)
• Calcitonin Gene-Related Peptide (metabolism, pharmacology)
• Calcitonin Gene-Related Peptide Receptor Antagonists
• Coronary Circulation
• Dopamine (analogs & derivatives, metabolism)
• Isoindoles (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardial Ischemia (complications, metabolism, physiopathology)
• Myocardial Reperfusion Injury (etiology, metabolism, physiopathology, prevention & control)
• Myocardium (metabolism)
• Neurokinin-1 Receptor Antagonists
• Peptide Fragments (pharmacology)
• Potassium Channel Blockers (pharmacology)
• Potassium Channels (metabolism)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Quaternary Ammonium Compounds (pharmacology)
• Radioimmunoassay
• Receptors, Calcitonin Gene-Related Peptide (metabolism)
• Receptors, Neurokinin-1 (metabolism)
• Substance P (metabolism)
• TRPV Cation Channels (deficiency, genetics, metabolism)
• Ventricular Function, Left
• Ventricular Pressure