Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle

• DOI: 10.1152/ajpcell.00629.2008
• Publication Date: 2009-11-05T03:39:28Z
• Authors: Wenju Lu; Pixin Ran; Dandan Zhang; Gongyong Peng; Bing Li; Nanshan Zhong; Jian Wang
• Keywords: Hypoxia; Hypoxic pulmonary vasoconstriction; TRPC6

In pulmonary arterial smooth muscle cells (PASMCs), Ca2+ influx through store-operated channels thought to be composed of canonical transient receptor potential (TRPC) proteins is an important determinant intracellular free calcium concentration ([Ca2+](i)) and vascular tone. Sildenafil, a type V phosphodiesterase inhibitor that increases cellular cGMP, recently identified as promising agent for treatment hypertension. We previously demonstrated chronic hypoxia elevated basal [Ca2+](i) in PASMCs due large part enhanced entry (SOCE); moreover, ex vivo exposure prolonged (4% O2 60 h) upregulated TRPC1 TRPC6 expression PASMCs. examined the effect sildenafil on [Ca2+](i), SOCE, TRPC under exposure. also (PA) from rats developed chronically hypoxic hypertension (CHPH). Compared with vehicle control, (300 nM) inhibited induced 1) 2) 3) mRNA protein Moreover, (50 mg . kg(-1) day(-1)) PA (10% 21 days) rats, which was associated decreased right ventricular pressure hypertrophy. Furthermore, we found, exposed hypoxia, knockdown or by their specific small interference RNA attenuated SOCE [Ca2+]i, suggesting cause link between [Ca2+]i. These results suggest may alter decreasing downregulation expression, thereby contributing tone arteries during development CHPH.