Rapid induction in-vitro of epithelial nitric-oxide synthase activity in guinea-pig isolated, perfused trachea by lipopolysaccharide.
FASEB J 1995 Mar; 9(3)(I):A147
The modulatory role of nitric oxide on reactivity of specific pathogen free guinea-pig airways to contractile agonists was examined using the isolated, perfused trachea. This preparation allows drugs to be applied separately to the serosal surface (the extraluminal or EL bath) where they have direct access to the smooth muscle, or to the mucosal surface (the intraluminal or IL bath), across which drugs must diffuse to reach the muscle. When either methacholine or histamine was administered to the IL bath, the nitric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME; 10(-4) M), significantly decreased reactivity. In the EL bath L-NAME was without effect. That is, L-NAME did not produce the characteristic potentiation of responses observed in many tissues. After 30 min incubation of the preparations in vitro with E. coli lipopolysaccharide (LPS; 10 microg/ml), the maximum responses to EL and IL methacholine and histamine were markedly decreased. Following LPS-exposure, L-NAME remained without effect on reactivity to EL methacholine, but produced a 3.2-fold increase in sensitivity to IL methacholine. These findings suggest that nitric oxide has little modulatory role in untreated guinea-pig airways. The potentiation of IL responses to methacholine by L-NAME after 30 min exposure to LPS suggests that NOS was rapidly induced in the respiratory epithelium.
Biochemical-analysis; Biochemistry; Biological-effects; Biological-systems; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cellular-reactions; Molecular-biology; Molecular-structure
The FASEB Journal. Experimental Biology 95 - Annual Meeting of Professional Research Scientists, Atlanta, Georgia, April 9-13, 1995