Open AccessProtective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity
Author(s) -
Beihua Zhong,
Shuangtao Ma,
Donna H. Wang
Publication year - 2020
Publication title -
cardiovasular and hematological disorders. drug targets
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.365
H-Index - 40
eISSN - 2212-4063
pISSN - 1871-529X
DOI - 10.2174/1871529x19666190912152041
Subject(s) - preload , calcitonin gene related peptide , medicine , trpv1 , endocrinology , reperfusion injury , capsaicin , ischemia , chemistry , hemodynamics , neuropeptide , receptor , transient receptor potential channel
Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1)channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing CalcitoninGene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study thecardioprotective effects of TRPV1 in obesity. Methods: TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet(HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo.The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) andreperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 μmol/L) and SP(0.1 μmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left VentricularDeveloped Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured. Results: HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in bothstrains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP,and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups.Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05).In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/-mice were improved by CGRP and SP. Conclusions: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinducedimpairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/-mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.