title: Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle.
abstract: The stretching of smooth muscle tissue modulates contraction through augmentation of Ca(2+) transients, but the mechanism underlying stretch-induced Ca(2+) transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at 30% and 18% beyond the initial length, respectively, resulted in Ca(2+) oscillations. Experiments indicated that mechanical stretching remarkably increased the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca(2+) oscillations and contractility increases were completely abolished by the NO inhibitor L-NAME or eNOS (also known as NOS3) gene inactivation. Moreover, exposure of eNOS-knockout myocytes to exogenous NO donor induced Ca(2+) oscillations. The stretch-induced Ca(2+) oscillations were greatly inhibited by the selective inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch-induced Ca(2+) oscillations were also suppressed by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that stretching myocyte and maintenance at a certain length results in Ca(2+) oscillations that are NO dependent , and sGC and cGMP independent, and results from the activation of PI3K in smooth muscle.
authors.affiliation: Urological Surgery Research Institute, Southwest Hospital, Third Military Medical University, Gao Tanyan Rd. 30, Chongqing 400038, China National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Rd, Beijing 100101, China.
authors.forename: Ji
authors.identifier: 0000-0002-4636-0998
authors.initials: J
authors.lastname: Zheng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Rd, Beijing 100101, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhai
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Rd, Beijing 100101, China.
authors.forename: Yingxiao
authors.identifier: 0000-0003-3521-6912
authors.initials: Y
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Rd, Beijing 100101, China.
authors.forename: Xu
authors.identifier: 0000-0003-4199-2029
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Rd, Beijing 100101, China.
authors.forename: Lin
authors.identifier: 0000-0002-3019-6628
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA gj28@ibp.ac.cn bwei@med.wayne.edu.
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Rd, Beijing 100101, China gj28@ibp.ac.cn bwei@med.wayne.edu.
authors.forename: Guangju
authors.identifier: 0000-0002-7536-500X
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D013314:Stress, Mechanical; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D006162:Guanylate Cyclase
keywords: Ca2+ oscillation; Ca2+ signaling; Nitric oxide; eNOS