Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle.
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.
['Zheng|Ji|J|0000-0002-4636-0998', 'Zhai|Kui|K|', 'Chen|Yingxiao|Y|0000-0003-3521-6912', 'Zhang|Xu|X|0000-0003-4199-2029', 'Miao|Lin|L|0000-0002-3019-6628', 'Wei|Bin|B|', 'Ji|Guangju|G|0000-0002-7536-500X']
D000818:Animals D020013:Calcium Signaling D004791:Enzyme Inhibitors D006162:Guanylate Cyclase D066298:In Vitro Techniques D053496:Inositol 1,4,5-Trisphosphate Receptors D018345:Mice, Knockout D009130:Muscle, Smooth D032389:Myocytes, Smooth Muscle D009569:Nitric Oxide D019869:Phosphatidylinositol 3-Kinases D013314:Stress, Mechanical D001743:Urinary Bladder
Nitric oxide Ca2+ oscillation eNOS Ca2+ signaling