Down-Regulation of TRPM8 in Pulmonary Arteries of Pulmonary Hypertensive Rats

Cellular Physiology and Biochemistry

关键词: Monocrotaline;    Chronic hypoxia;    Menthol;    Transient receptor potential melastatin;    Pulmonary hypertension;    Calcium signaling;   

DOI  :  10.1159/000350107

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND