BOMBESIN-INDUCED CONTRACTIONS OF GUINEA-PIG LUNG STRIPS ARE MODULATEDBY ENDOGENOUS NITRIC-OXIDE

We have investigated the effects of a nitric oxide (NO) biosynthesis i nhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on the bombesi n-evoked contraction of guinea pig parenchymal lung strips. The bombes in-induced contractions of lung strips were significantly increased af ter L-NAME (300 mu M) pre-treatment. The maximal response was increase d (P < 0.01) by 37% after L-NAME treatment when compared with the cont rol group. The pD(2) value was not influenced by L-NAME pre-treatment. The enhancement of the bombesin-induced contraction caused by L-NAME was reversed by addition of an excess of the NO precursor -L-arginine (600 mu M) but not by the addition of its inactive enantiomer D-argini ne (600 mu M). Like L-NAME, methylene blue (1 mu M), an agent that inh ibits the soluble guanylyl cyclase activated by NO, significantly incr eased (P < 0.01) the maximal contraction induced by bombesin (183 +/- 16 mg) when compared with the control group (141 +/- 15 mg). When test ed against other agonist-induced contractions, L-NAME did not change t he responsiveness of parenchymal lung strips to bradykinin or carbacho l but significantly increased the lung contraction induced by histamin e. NO synthesis inhibition resulted in a pronounced increase in the bo mbesin-induced contraction of guinea-pig lung strips. Our results sugg est that bombesin contributes to NO synthesis and release which then a cts to reduce the contraction of the lungstrip in response to bombesin .