Key roles of nitric oxide and cyclic GMP in nonadrenergic and noncholinergic inhibition in rat ileum.

Nonadrenergic and noncholinergic (NANC) inhibitory responses in circular and longitudinal muscles of the rat ileum were studied separately in vitro. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. Nitro-arginine inhibited the relaxation and L-arginine counteracted the effect of nitro-arginine. Treatment of the preparation with superoxide dismutase (SOD) and methylene blue resulted in enhancement and inhibition, respectively, of the relaxation induced by distension. Nitric oxide caused relaxation of the circular muscle in a dose-dependent manner. 8-Bromo cyclic GMP (cGMP) caused relaxation of the circular muscle. Electrical transmural stimulation caused relaxation followed by a rebound contraction of the longitudinal muscle. Nitro-arginine inhibited the relaxation and L-arginine counteracted this inhibition. Similar results to those in the circular muscle were obtained in the longitudinal muscle with SOD, methylene blue, nitric oxide and 8-bromo cGMP. Electrical field stimulation increased the cGMP content of the longitudinal muscle preparation. Nitric oxide also increased the cGMP content of smooth muscle cells obtained from circular and longitudinal muscles of rat ileum. Preincubation of smooth muscle cells with methylene blue inhibited the effect of nitric oxide on the cGMP content. These results suggest a key role of cGMP in NANC inhibitory responses in rat ileum. The factors mediating the responses are discussed.