Alterations of TRPC1 Expression and Store‐Operated Ca2+ Entry in Pulmonary Arteries of Monocrotaline‐Induced Pulmonary Hypertensive Rats

Abstract

Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that chronic hypoxia upregulates canonical transient receptor potential (TRPC) genes and enhances store-operated Ca2+ entry (SOCE) in PASMCs. Similar changes have not been examined in monocrotaline (MCT)-induced PH. Here PH was induced in rats by a single intraperitoneal injection of MCT. MCT-injected rats developed severe PH and right ventricular hypertrophy within three weeks. qRT-PCR and western blot showed that the expression of mRNA and protein of the store-operated TRPC1 channel were increased in pulmonary arteries (PAs) of MCT-treated rats. Activation of SOCE with cyclopiazonic acid evoked contraction of isolated PAs and Ca2+ influx in PASMCs of control rats, which were dramatically enhanced in MCT-treated animals. Moreover, endothelin-1 elicited vasoconstriction was potentiated in PAs of MCT-treated rats, and the responses were more susceptible to La3+ (30 μM) inhibition, which blocks SOCE. Our results showed that the alterations of TRPC1 expression and SOCE activity in PAs of MCT-treated rats are similar to chronic hypoxic rats, suggesting that the TRPC1-SOCE pathway might be a pivotal common mechanism in the pathogenesis of PH. (supported by NSFC 30670772, FJMU09ZD010, NSF-Fujian 2010J01173, and R01-HL075134)