Down-regulation of TRPM8 in pulmonary arteries of pulmonary hypertensive rats

Xiao Ru Liu, Qing Liu, Gai Ying Chen, Ying Hu, James S.K. Sham, Mo Jun Lin

Research output: Contribution to journalArticle

Abstract

Background: Pulmonary hypertension (PH) is characterized by profound vascular remodeling and alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Multiple transient receptor potential melastatin-related (TRPM) subtypes have been identified in vascular tissue. However, the changes in the expression and function of TRPM channels in pulmonary hypertension have not been characterized in detail. Methods: We examined the expression of TRPM channels and characterized the functions of the altered TRPM channels in two widely used rat models of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH. Results: CH-exposed and MCT-treated rats developed severe PH and right ventricular hypertrophy, with a significant decrease in TRPM8 mRNA and protein expression in pulmonary arteries (PAs). The downregulation of TRPM8 was associated with significant reduction in menthol-induced cation-influx. Time-profiles showed that TRPM8 down-regulation occurred prior to the increase of right ventricular systolic pressure (RVSP) and right ventricular mass index (RVMI) in CH-exposed rats, but these changes were delayed in MCT-treated rats. The TRPM8 agonist menthol induced vasorelaxation in phenylephrine-precontracted PAs, and the vasorelaxing effects were significantly attenuated in PAs of both PH rat models, consistent with decreased TRPM8 expression. Conclusion: Downregulation of TRPM8 may contribute to the enhanced vasoreactivity in PH.

Original languageEnglish (US)
Pages (from-to)892-904
Number of pages13
JournalCellular Physiology and Biochemistry
Volume31
Issue number6
DOIs
StatePublished - Jul 2013

Keywords

  • Calcium signaling
  • Chronic hypoxia
  • Menthol
  • Monocrotaline
  • Pulmonary hypertension
  • Transient receptor potential melastatin

ASJC Scopus subject areas

  • Physiology

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