Alteration of serotonin 2C receptor expression in the aorta and the pulmonary artery in rats exposed to hypoxia.

In the present study we reported the expression of the 5-HT2C receptor (5-HT2C-R) in the aorta and the pulmonary artery in rats exposed to hypoxia, and examined its role in vascular smooth muscle cells. Immunochemistry, quantitative RT-PCR, and western blot were used to examine 5-HT2C-R expression. Small interfering RNA (siRNA) was used to explore the role of 5-HT2C-R in vascular smooth muscle cells proliferation and contraction induced by 5-HT.5-HT2C-R immunoreactivity was confined predominantly to the plasma membrane in the rat aortic smooth muscle cells (ASMCs) and the pulmonary arterial smooth muscle cells (PASMCs). 5-HT2C-R mRNA expression in the aorta of hypoxic pulmonary hypertension (HPH) rats was more than that in the pulmonary artery. Hypoxia-induced 5-HT2C-R protein expression in the aorta was less than that in the pulmonary artery, indicating that 5-HT2C-R might mediate different responses of the aorta and the pulmonary artery to 5-HT in HPH. We also demonstrated that RNA editing may not be involved in the different expression levels of 5-HT2C-R in the aorta and the pulmonary artery. The higher expression of 5-HT2C-R in the pulmonary artery versus the aorta of HPH rats was partly due to the increased protein stability. siRNA was used to knock down the expression of 5-HT2C-R. 5-HT2C-R-specific siRNA reduced the proliferation and contraction of vascular smooth muscle cells induced by 5-HT. In conclusion, the different expression patterns of 5-HT2C-R protein in the aorta and the pulmonary artery suggest that this 5-HT receptor may be involved, at least partly, in modulating different responses of systemic vessels and pulmonary vasculature to 5-HT in HPH.