THE INVOLVEMENT OF NITRIC-OXIDE SYNTHASE IN THE EFFECT OF HISTAMINE ON GUINEA-PIG AIRWAY SMOOTH-MUSCLE IN-VITRO

The influence of histamine on nitric oxide synthase (NOS) in the development of airway smooth muscle hyperresponsiveness to histamine was investigated in vitro. In the absence of histamine, N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M) had no significant effect on the basal tone. However, precontraction of the tissues with histamine (0.3 mu M) resulted in a significant contractile response to L-NAME in the preparations with intact, epithelium. Removal of the epithelial layer decreased the responses to L-NAME. L-arginine could partially reverse the contraction produced by L-NAME. L-NAME enhanced the maximal response to histamine, but the sensitivity of the tracheal smooth muscle to histamine was not affected. These results suggest that, in the airway, histamine can activate NOS, resulting in the release of nitric oxide. The latter may be regarded as a local negative modulator to maintain the tissue in a physiological homeostasis.