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Hypoxic Preconditioning Protects Rat Hearts Against Ischemia/Reperfusion Injury via H 2 S/TRPA1 Pathway
Author(s) -
Ma MingChieh,
Huang HoShiang,
Chen YihSharng
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb648
Subject(s) - cardioprotection , ischemic preconditioning , cystathionine beta synthase , chemistry , calcitonin gene related peptide , pharmacology , ischemia , blockade , receptor , medicine , biochemistry , neuropeptide , cysteine , enzyme
Hypoxic preconditioning (HPC) protects rat hearts against ischemia/reperfusion (IR) injury. The Ca 2+ ‐permeable transient receptor potential ankyrin 1 (TRPA1) is present in cardiac tissue and plays an important on blood pressure regulation. However, the role of TRPA1 in HPC‐mediated cardioprotection remains unknown. TRPA1 can be activated by a novel gasotransmitter hydrogen sulfide (H 2 S), which is synthesized endogenously by cystathionine β‐synthase (CBS) and cystathionine γ‐lyase (CSE). Here we examined whether HPC protects the myocardium against IR via the H 2 S/TRPA1 pathway. Compared to hearts of rats kept in room air, the hearts of rats kept in air preconditioned with 10% oxygen for 4 weeks had better post‐ischemic recovery and less tissue damage when subjected to 30‐min stop of perfusion and 4‐h reflow in a Langendorff apparatus. HC030031, a selective TRPA1 blocker, administered 5 min before reperfusion markedly attenuated the effects of HPC, confirming TRPA1 is a downstream effector in HPC‐mediated cardioprotection. Additionally, HPC markedly increased calcitonin gene‐related peptide (CGRP) and substance P (SP) release in coronary perfusate, which could be reversed by TRPA1 blockade, but not CGRP receptor or SP receptor inhibition. HPC resulted in the upregulation of CBS and CSE, and H 2 S levels in coronary perfusate, and prevented IR‐induced H 2 S reduction. Blockade of CBS and CSE by aminooxyacetic acid (AOAA) abrogated the effects of HPC and lowered release of H 2 S, CGRP, and SP. Mimicking the effects of HPC by given Na 2 S or NaHS to the AOAA‐treated hearts enhanced cardiac recovery and neuropeptide release during reperfusion. Our results demonstrate that HPC reduces heart susceptibly to IR via the H 2 S/TRPA1/neuropeptide pathway, as shown by increased enzyme responsible for H 2 S formation in HPC hearts. Support or Funding Information This study was supported by the Ministry of Science and Technology R.O.C. (MOST105‐2314‐B‐030‐009).