Open AccessInositol 1,4,5‐Trisphosphate Receptors in Endothelial Cells Play an Essential Role in Vasodilation and Blood Pressure Regulation
Author(s) -
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
Publication year - 2019
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.118.011704
Subject(s) - vasodilation , microbiology and biotechnology , endothelial stem cell , endoplasmic reticulum , endothelium , inositol , biology , endocrinology , receptor , medicine , chemistry , biochemistry , in vitro
Background Endothelial NO synthase plays a central role in regulating vasodilation and blood pressure. Intracellular Ca 2+ mobilization is a critical modulator of endothelial NO synthase function, and increased cytosolic Ca 2+ concentration in endothelial cells is able to induce endothelial NO synthase phosphorylation. Ca 2+ release mediated by 3 subtypes of inositol 1,4,5‐trisphosphate receptors ( IP 3 Rs) from the endoplasmic reticulum and subsequent Ca 2+ entry after endoplasmic reticulum Ca 2+ store depletion has been proposed to be the major pathway to mobilize Ca 2+ 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 IP 3 R triple knockout mice and found that deletion of all 3 IP 3 R subtypes decreased plasma NO concentration and increased basal blood pressure. Furthermore, IP 3 R deficiency reduced acetylcholine‐induced vasodilation and endothelial NO synthase phosphorylation at Ser1177. Conclusions Our results reveal that IP 3 R‐mediated Ca 2+ release in vascular endothelial cells plays an important role in regulating vasodilation and physiological blood pressure.