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 devel opment of airway smooth muscle hyperresponsiveness to histamine was in vestigated 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 basa l tone. However, precontraction of the tissues with histamine (0.3 mu M) resulted in a significant contractile response to L-NAME in the pre parations with intact, epithelium. Removal of the epithelial layer dec reased 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 his tamine was not affected. These results suggest that, in the airway, hi stamine can activate NOS, resulting in the release of nitric oxide. Th e latter may be regarded as a local negative modulator to maintain the tissue in a physiological homeostasis.