Cardioprotective Effect of Capsaicin Against Myocardial Ischemia–Reperfusion Injury in a Diabetic Rat Model via Activation of the TRPV1-CGRP Pathway

The transient receptor potential vanilloid type 1 (TRPV1) channel has been implicated in the regulation of myocardial ischemia/reperfusion (I/R) injury. Previous studies have demonstrated a reduction in TRPV1 function in cardiomyocytes from diabetes mellitus models. This study aims to determine the contribution of reduced TRPV1 expression in the exacerbation of myocardial I/R injury in a diabetic state and to evaluate the cardioprotective effects of capsaicin through TRPV1 activation. Male Sprague–Dawley rats were randomly divided into four groups: control (C), control treated with capsaicin (C + cap), diabetes mellitus (DM), and DM treated with capsaicin (D + cap). Diabetes was induced via intraperitoneal injection of streptozotocin at a dose of 50 mg/kg. The C + cap and D + cap groups received a standard laboratory diet supplemented with 0.0174% capsaicin. Myocardial infarct size, apoptosis rate of cardiomyocytes, and the levels of TRPV1, CGRP (calcitonin gene-related peptide), Caspase-3, and cardiac troponin I (cTnI) were assessed. Rats in the DM group exhibited a significantly larger myocardial infarct size in both in vivo and in vitro assessments compared to the control group. Additionally, increased apoptosis rates, elevated Caspase-3 levels, and higher serum cTnI concentrations were observed in the DM group. The expression levels of TRPV1 and CGRP in myocardial tissue were significantly reduced in the DM group compared to the C group. In contrast, the D + cap group exhibited a significant reduction in infarct size, apoptosis, Caspase-3 levels, and serum cTnI levels compared to the DM group. Furthermore, TRPV1 and CGRP expression levels were significantly enhanced in the myocardium of the D + cap group compared to the DM group. Diabetes mellitus was associated with increased susceptibility to myocardial I/R injury, accompanied by reduced TRPV1 expression and diminished CGRP levels in cardiac tissue. Capsaicin, acting as a TRPV1 agonist, enhanced TRPV1 activation and CGRP release from cardiac sensory neurons, thereby mitigating myocardial I/R injury. These findings suggest a potential therapeutic role for capsaicin in the treatment of myocardial ischemic injury in the context of diabetes.