Issue Archive

[TRPC6 mediates the enhancements of pulmonary arterial tone and intracellular Ca2+ concentration of pulmonary arterial smooth muscle cells in pulmonary hypertension rats.] [Ariticle in Chinese]

ZHANG Ming-Fang, LIU Xiao-Ru, YANG Na, LIN Mo-Jun

Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou 350004, China

Abstract

Pulmonary arterial hypertension is associated with profound vascular remodeling and alterations in Ca2+ homeostasis inpulmonary arterial smooth muscle cells (PASMCs). Recent studies show that canonical transient receptor potential channel 6 (TRPC6)genes, which encode receptor-operated cation channels (ROCC) in PASMCs, play an important role in Ca2+ regulation and cellproliferation. The aim of the present study was to investigate the role of TRPC6 in monocrotaline (MCT)-induced pulmonary arteryhypertension. Sprague-Dawley rats were randomly divided into normal control group and MCT group. In MCT group, pulmonaryarterial hypertension was induced by a single intraperitoneal injection of MCT at a dose of 60 mg/kg. After 3 weeks, the right ventricularsystolic pressure (RVSP) and the right ventricular mass index (RVMI) were measured. The lung sections were stained by HE andobserved under light microscope. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot wereperformed to detect the expression of TRPC6 in rat pulmonary arteries. The 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced contractiletension of pulmonary arteries were measured by vascular ring tension analysis and the intracellular Ca2+ concentration ([Ca2+]i)of PASMCs was monitored using Fluo3-AM assay. The results showed that RVSP and RVMI markedly elevated in MCT group (P<0.01)in comparison to CON group. The thickness of pulmonary vascular smooth muscles was increased and the inner diameter of pulmonaryarteries was diminished in MCT group. Though there was no significant difference in the levels of mRNA and protein of TRPC6between CON and MCT groups, the application of OAG, which can directly activate ROCC, induced greater contraction tension ofpulmonary arteries (P<0.01) and more Ca2+ entries in PASMCs (P<0.05) in MCT group compared to those in control group. Theseresults indicate that MCT induces pulmonary artery hypertension and thus remodeling of the right ventricle and pulmonary arteries inrats. The expression of mRNA and protein of TRPC6 is not potentiated by MCT, but the TRPC6/ROCC-mediated Ca2+ entry inPASMCs and vascular tone of pulmonary arteries are significantly increased with MCT treatment.

Key words: pulmonary arterial hypertension; transient receptor potential channels; Ca2+; receptor-operated Ca2+ channel

Received: 2009-09-22　　Accepted: 2009-12-18

Corresponding author: 　　E-mail:

Citing This Article：

ZHANG Ming-Fang, LIU Xiao-Ru, YANG Na, LIN Mo-Jun. [TRPC6 mediates the enhancements of pulmonary arterial tone and intracellular Ca2+ concentration of pulmonary arterial smooth muscle cells in pulmonary hypertension rats.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (1): 55-62 (in Chinese with English abstract).