Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth muscle

Bradykinin (10^–8-10^–5M) caused a concentration-dependent increase in cyclic GMP (cGMP) production in bovine tracheal smooth muscle in the absence of epithelium. The effect was calcium-dependent and was inhibited by pyrogallol (10 M) and methylene blue (10 M). The inhibition of pyrogallol was reversed by superoxide dismutase (100 Usnowml). Nitric oxide (NO) synthase inhibitors, N ^G-methyl-l-arginine (10–100 M) and N ^G-nitro-l-arginine (10–100 M) reduced cGMP accumulation induced by bradykinin in a concentration-dependent fashion, and the inhibition was reversed by l-arginine. Immunohistochemistry with a specific antibody against neuronal NO synthase from rat cerebellum showed positive staining localized in some nerve fibers. Bradykinin-induced cGMP accumulation appears to be related to the release of NO, part of which is probably synthesized in nonadrenergic noncholinergic nerve in bovine trachea.Offprint requests to: Dr. Hong Sheng