Involvement Of Vanilloid Receptors In The Depressor And Cardioprotective Effects Induced By Rutaecarpine

Part I Involvement of vanilloid receptors in heat stress-induced delayed cardioprotection in rats BACKGROUNDCapsaicin receptor (or vanilloid receptor 1, VRi) has been identified in peripheral and central terminals as well as in cell bodies of primary sensory neurons. VRi is non-selective cation channel directly activated by injurious heat, extracelluar protons and vanilliod compounds and can be viewed as a molecular integrator of some injurious stimuli. It has been indicated that sublethal hyperthermia protects the myocardium against injury, due to ischemia-reperfusion and that the delayed cardioprotection afforded by heat stress involves the synthesis and release of calcitonin" gene-related peptide (CGRP), a principal transmitter in sensory nerves. Studies in vitro and in vivo have shown that VRi mediates the release and synthesis of sensory neurotransmitters. It is probable that the delayed cardioprotective effects afforded by heat stress are related to the resultant synthesis and release of endogenous CGRP by direct activation of VRi. Since capsazepine is a competitive VRi antagonist, in the present study, we have used capsazepine to indicate whether the cardioprotection conferred by heat stress is a consequence of specific receptor interaction.METHODSRats were pretreated with whole body hyperthermia (rectal 42C) for 15 min, 24 h before the experiments, and then the left main coronary artery of rat hearts was subjected to a 60-min occlusion followed by 3-h reperfusion. Myocardium injury degree was evaluated by measurement of infarct size and serum creatine kinase (CK) activity. Plasma concentrations of CGRP, and the expression of a- and (5-CGRP rnRNA in dorsal root ganglia were determined by radioimmunoassay and semi-quantitative reverse-transcription polymerase chain reaction, respectively. The experimen was divided into six group: (1) sham; (2) ischernia-reperfusion; (3) heat stress; (4) Capsazepine + heat stress: capsazepine (38 mg/kg, s.c.) was administered 60 min before heat stress; (5) Vehicle (capsazepine) + heat stress; (6) Capsazepine.RESULTSHyperthermia treatment significantly reduced infarct size and CK release concomitantly with a dramatic increase in plasma concentrations of CGRP and the expression of cc-CGRP mRNA, but not {3-CGRl> mRNA, which was completely abolished by pretreatment with capsazepine.CONCLUSIONThese results suggests that the delayed cardioprotection induced byheat stress is related to stimulation of endogenous a-CGRP release via activating vanilloid receptors in rats.