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 th e absence of epithelium. The effect was calcium-dependent and was inhi bited by pyrogallol (10 mu M) and methylene blue (10 mu M). The inhibi tion of pyrogallol was reversed by superoxide dismutase (100 U/ml). Ni tric oxide (NO) synthase inhibitors, N-G-methyl-L-arginine (10-100 mu M) and N-G-nitro-L-arginine (10-100 mu M) reduced cGMP accumulation in duced by bradykinin in a concentration-dependent fashion, and the inhi bition was reversed by L-arginine. Immunohistochemistry with a specifi c antibody against neuronal NO synthase from rat cerebellum showed pos itive staining localized in some nerve fibers. Bradykinin-induced cGMP accumulation appears to be related to the release of NO, part of whic h is probably synthesized in nonadrenergic noncholinergic nerve in bov ine trachea.