Nonadrenergic, noncholinergic relaxation mediated by nitric oxide with concomitant change in Ca 2+ level in rectal circular muscle of rats

Abstract

The mediators of nonadrenergic, noncholinergic (NANC) relaxation of the circular muscle of rat rectum were examined in vitro. In the circular muscle of rat rectum, N G-nitro- l-arginine ( l-NOARG) at 10 μM did not affect electrical field stimulation-induced relaxation but at 100 μM it inhibited electrical field stimulation-induced relaxation by about 75% and 1-mM l-arginine reversed the inhibition. Exogenous nitric oxide (NO) (1–10 μM) concentration dependently relaxed the circular muscle. Electrical field stimulation increased the cyclic GMP content of the circular muscle to about twice its resting level. l-NOARG, even at 10 μM, completely inhibited the electrical field stimulation-induced elevation of cyclic GMP content. However, l-arginine at 1 mM did not reverse the inhibition in cyclic GMP content. Inhibitory junction potentials (i.j.ps) induced by electrical field stimulation in the circular muscle cells were not affected by l-NOARG, 100 μM. Apamin (≤1 μM) did not affect the electrical field stimulation-induced relaxation, but almost completely inhibited electrical field stimulation-induced i.j.ps. NO (0.3–10 μM) induced relaxation of the circular muscle with a concomitant decrease in intracellular Ca 2+ level ([Ca 2+] i). Abundant immunoreactivity of NO synthase was found in the circular muscle layer, in addition to myenteric and submucosal plexus. The results suggest that NO induces NANC relaxation with a concomitant change in [Ca 2+] i in the circular muscle of rat rectum. However, the involvement of changes in cyclic GMP level and in membrane potentials in the mechanism was not shown in the present experimental conditions.