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.

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

“…25,27 The protein S-nitrosylation reaction (in which NO reacts with cysteine thiols to form S-nitrosylated proteins) is an important posttranslational modification and thus regulates protein structures and functions. 33,[39][40][41] which may cause significant oxidative damage on various target biomolecules, such as lipids, sugars, DNA, and proteins. 25,42 Functions of the NO System Inside Dental Pulp Tissue and the Involved Mechanisms…”

Optimal vacuum erectile device therapy regimen for penile rehabilitation in a bilateral cavernous nerve crush rat model

“…When the VED therapy duration was 4–8 min, there was no significant difference in SO 2 , pO 2 , and Arterial% of the corpus cavernosum. A plateau was observed and this plateau might be due to the fact that VED tension induced the release of NO from endothelial cells, which promoted the further relaxation of vascular smooth muscle and maintained the oxygen balance 25 . After VED therapy exceeded 10 min, the Arterial% and pO 2 levels decreased in a time‐dependent manner, which might be related to the increase of oxygen consumption and venous blood filling in the corpus cavernosum 24 .…”

Acute Effects of Nitrate-Rich Beetroot Juice on Blood Pressure, Hemostasis and Vascular Inflammation Markers in Healthy Older Adults: A Randomized, Placebo-Controlled Crossover Study

“…The VLF domain has been linked to the myogenic response of the vasculature [ 17 ]. Previous animal data have suggested that NO mediated smooth muscle contraction through Ca 2+ oscillation [ 28 ], whereas a more recent human study showed that dietary nitrate increased skeletal muscle force without changing calcium handling [ 29 ]. Whether our data are reflective of an increased myogenic vascular responsiveness needs to be addressed in future studies.…”