Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1)
channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin
Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the
cardioprotective 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) and
reperfusion (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 Ventricular
Developed 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 both
strains (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.
Conclusion: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced
impairment 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.