Induction of nitric oxide synthase in rabbit intrapulmonary arteries by interleukin 1β

The effect of interleukin-1B (IL-1β) on the contractility of rabbit intrapulmonary arteries was studied under in vitro conditions. Isolated vessels were mounted in standard tissue baths and served either as control vessels or as test vessels that were incubated with 400 IU/ml of IL-1β for 4 hours. A comparison of subsequent phenylephrine (10^-8-10^-5M) concentrationresponse curves between control and test arteries revealed that IL-1β significantly depressed the contractile response to all concentrations of phenylephrine in both endothelium-intact and endothelium-removed arteries. The addition of either 2×10^-6M actinomycin-D, a transcription inhibitor, or 3 × 10^-4 M N^G-nitro-L-arginine (LNA), a nitric oxide synthase inhibitor, 30 minutes prior to incubation with IL-1β abolished the inhibitory effect of IL-1β on phenylephrine-induced contractions. The effect of LNA on contractions induced by 3 × 10^-5 M phenylephrine also was examined after incubation with IL-1β. LNA caused 19 ± 3 % and 1 ± 1 % increases in the force of phenylephrine-induced contractions of control endothelium-inlact and endothelium-removed arteries, respectively. LNA caused 96 ± 16 % and 42 ± 15 % increases in the force of phenylephrine-induced contractions of IL-1β treated endothelium-intact and endothelium-removed arteries, respectively. It is concluded that IL-1β inhibits contraction of rabbit intrapulmonary arteries by increasing the production of nitric oxide via the induction of iNOS in vascular smooth muscle as well as endothelial cells.