| Title | Inositol 1,4,5-Trisphosphate Receptors in Endothelial Cells Play an Essential Role in Vasodilation and Blood Pressure Regulation |
| Authors | Lin, Qingsong Zhao, Lingyun Jing, Ran Trexler, Christa Wang, Hong Li, Yali Tang, Huayuan Huang, Fang Zhang, Fei Fang, Xi Liu, Jie Jia, Nan Chen, Ju Ouyang, Kunfu |
| Affiliation | Peking Univ, Sch Chem Biol & Biotechnol, Drug Discovery Ctr, State Key Lab Chem Oncogen,Shenzhen Grad Sch, Shenzhen, Peoples R China Cent S Univ, Xiangya Hosp 2, Dept Cardiol, Changsha, Hunan, Peoples R China Univ Calif San Diego, Sch Med, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA Shenzhen Univ, Sch Med, Dept Pathophysiol, Shenzhen, Peoples R China Sun Yat Sen Univ, Affiliated Hosp 8, Dept Cardiol, Shenzhen, Peoples R China |
| Keywords | blood pressure calcium calcium signaling endothelial cell hypertension |
| Issue Date | 2019 |
| Publisher | JOURNAL OF THE AMERICAN HEART ASSOCIATION |
| Abstract | Background-Endothelial NO synthase plays a central role in regulating vasodilation and blood pressure. Intracellular Ca2+ mobilization is a critical modulator of endothelial NO synthase function, and increased cytosolic Ca2+ concentration in endothelial cells is able to induce endothelial NO synthase phosphorylation. Ca2+ release mediated by 3 subtypes of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) from the endoplasmic reticulum and subsequent Ca2+ entry after endoplasmic reticulum Ca2+ store depletion has been proposed to be the major pathway to mobilize Ca2+ in endothelial cells. However, the physiological role of IP(3)Rs in regulating blood pressure remains largely unclear. Methods and Results-To investigate the role of endothelial IP(3)Rs in blood pressure regulation, we first generated an inducible endothelial cell-specific IP(3)R1 knockout mouse model and found that deletion of IP(3)R1 in adult endothelial cells did not affect vasodilation and blood pressure. Considering all 3 subtypes of IP(3)Rs are expressed in mouse endothelial cells, we further generated inducible endothelial cell-specific IP3R triple knockout mice and found that deletion of all 3 IP3R subtypes decreased plasma NO concentration and increased basal blood pressure. Furthermore, IP3R deficiency reduced acetylcholine-induced vasodilation and endothelial NO synthase phosphorylation at Ser1177. Conclusions-Our results reveal that IP3R-mediated Ca2+ release in vascular endothelial cells plays an important role in regulating vasodilation and physiological blood pressure. |
| URI | http://hdl.handle.net/20.500.11897/550602 |
| ISSN | 2047-9980 |
| DOI | 10.1161/JAHA.118.011704 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 化学生物学与生物技术学院 å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
