| Backgroud:Myocardial ischemia causes the release of protons and bradykinin, which activate transient receptor potential vanilloid 1 (TRPV1) channel expressed in cardiac sensory nerve terminals, to cause angina. Our previous study found that ischemia induced TRPV1 activation and consequent sensory neurotransmitter substance P (SP) release plays a protective role in heart function. However, whether SP mediate TRPV1 protective role in apoptosis is unclear.Object:The aim of this study is to investigate whether SP mediates the protective role of TRPV1 in apoptosis post myocardial infarction.Methods:In this study, myocardial infarction (MI) models were established in wild type (WT) and TRPVl-null mutant (TRPV1-/-) mice. SP and RP67580 (a NK1 receptor antagonist) were pretreated before MI. The infarct size was detected by TTC stain; the apoptosis index was determined by TUNEL; the expression of caspase-3, Bcl-2, Bax and p53 were detected by Western blot 24 hours post myocardial infarction.Results:Compared with sham group, infarct size, apoptosis index, caspase-3 activity were increased post MI in both TRPV1-/- and WT mice. The expression levels of p53 and Bcl-2/Bax were decreased in both strains after MI. TRPV1-/- mice presented a greater infarct size, apoptosis index, elevated activity of caspase-3, and lower expression of p53 and Bcl-2/Bax, compared with WT mice. Pretreatment with substance P, the Bcl-2/Bax and activity of caspase-3 were increased in both strains, and more significant changes were showed in TRPV1-/- mice. However, the administration of SP significant decreased the infarct size and apoptosis index in TRPV1-/- mice but not in WT mice. Blockade of the NK1 receptor with RP67580 increased the infarct size, apoptosis index, Bcl-2/Bax and increased activity of caspase-3 in both strains, compared with corresponding control group.Conclusion:These data show that SP may mediate the protective role of TRPV1 in apoptosis post acute myocardial infarction. |
PDF Full Text Request