Down-Regulation of TRPM8 in Pulmonary Arteries of Pulmonary Hypertensive Rats
| Autor: | Xiao-Ru Liu, Qing Liu, Gai-Ying Chen, Ying Hu, James S.K. Sham, Mo-Jun Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 31, Iss 6, Pp 892-904 (2013) |
| Druh dokumentu: | article |
| ISSN: | 1015-8987 1421-9778 |
| DOI: | 10.1159/000350107 |
| Popis: | Background: Pulmonary hypertension (PH) is characterized by profound vascular remodeling and alterations in Ca2+ 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. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|