Mechanism underlying the negative inotropic effect in rat left ventricle in hyperthermia: the role of TRPV1

• Published in: The journal of physiological sciences Vol. 70; no. 1; p. 4
• Main Authors: Obata, Koji, Morita, Hironobu, Takaki, Miyako
• Format: Journal Article
• Language: English
• Published: Japan Springer 05.02.2020; BioMed Central
• Subjects: Antibodies; Blood pressure; Calcium; Capsaicin; Capsaicin receptors; Capsazepine; Fever; Heart; Hyperthermia; Kinases; Laboratory animals; Metabolism; Muscle contraction; Original Paper; Oxygen consumption; Phospholamban; Phosphorylation; Serine; Signal transduction; Software; Variance analysis; Ventricle; Japan; United Kingdom > UK; LV contractility; Oxygen consumption; TRPV1; Excitation–contraction coupling; Hyperthermia
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1186/s12576-020-00734-5

We have previously reported that the negative inotropic effects of hyperthermia (42 °C) on left ventricular (LV) mechanoenergetics using the excised, cross-circulated rat heart model. Here, we investigated the role of TRPV1 on LV mechanoenergetics in hyperthermia. We analyzed the LV end-systolic pressure-volume relation (ESPVR) and the linear relation between the myocardial oxygen consumption per beat (VO ) and the systolic pressure-volume area (PVA; a total mechanical energy per beat) during infusion of capsazepine (CPZ) in hyperthermia, or capsaicin (Cap) under 300 bpm pacing. LV ESP decreased in each LV volume and the resultant downward-shift of LV ESPVR was suppressed by CPZ infusion in hyperthermia-hearts. In Cap-treated hearts, LV ESPVR shifted downward from the control ESPVR, similar to hyperthermia-hearts. The slopes of VO -PVA relationship were unchanged. The VO intercepts in hyperthermia-hearts did not decrease because of decreased E-C coupling VO , and inversely increased basal metabolic VO , which was suppressed by CPZ, though the VO intercepts in Cap-treated hearts significantly decreased. The levels of phosphorylated phospholamban at serine 16 decreased significantly in hyperthermia-hearts, as well as Cap-treated hearts. These results indicate that a Cap-induced decrease in the LV contractility, like in cases of hyperthermia, are due to the down-regulation of the total calcium handling in E-C coupling, suggesting that negative inotropic effect in hyperthermia-heart is, at least in part, mediated through TRPV1 signaling pathway.