Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle

Abstract

The stretching of smooth muscle tissue modulates contraction via augmentation of Ca2+ transients, but the mechanism underlying stretch-induced Ca2+ transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at the initial length of 30% and 18%, respectively, resulted in Ca2+ oscillations. Experiments indicated that mechanical stretching remarkably increases the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca2+ oscillations and contractility increases were completely abolished by NO inhibitor L-NAME or eNOS gene inactivation. Moreover, exposure of eNOS knockout myocytes to exogenous NO donor induced Ca2+ oscillations. The stretch-induced Ca2+ oscillations were greatly inhibited by selective IP3R inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch-induced Ca2+ oscillations were also suppressed by LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that myocytes stretching and maintenance at a certain length resulted in Ca2+ oscillations that is NO dependent and sGC/cGMP independent and results from the activation of PI(3)K in smooth muscle.