891.
The influence of histamine on nitric oxide synthase (NOS) in the development of airway smooth muscle hyperresponsiveness to histamine was investigatedin vitro. In the absence of histamine,N
G-nitro-l-arginine methyl ester (l-NAME, 100 μM) had no significant effect on the basal tone. However, precontraction of the tissues with histamine (0.3 μM) resulted in a significant contractile response tol-NAME in the preparations with intact epithelium. Removal of the epithelial layer decreased the responses tol-NAME.l-arginine could partially reverse the contraction produced byl-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.
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