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

Bradykinin (10(-8) - 10(-5) M) 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 microM) and methylene blue (10 microM). The inhibition of pyrogallol was reversed by superoxide dismutase (100 U/ml). Nitric oxide (NO) synthase inhibitors, NG-methyl-L-arginine (10-100 microM) and NG-nitro-L-arginine (10-100 microM) 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.