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Both U-74006F and Dexamethasone Inhibit Interleukin-1β Induced Vascular Smooth Muscle Oscillations

並列摘要


Background: Incubation of aortic rings with interleukin-1β (IL-1β) induces spontaneous oscillation during phenylephrine-induced contraction. We hypothesized that the steroid compounds, U-74006F and dexamethasone could inhibit the induction of inducible nitric oxide synthase (iNOS) and further inhibit this oscillation. Methods: Rat aortic rings (endothelium removed) were incubated in IL-1β with or without the non-glucocorticoid 21-aminosteroid U-74006F (10^(-6) M) or the glucocorticoid dexamethasone (10^(-6) M) for 3, 5 or 7 hours. Spontaneous oscillation was induced by contraction with phenylephrine. Results: Oscillation occurred during phenylephrine-induced contraction and Larginine-induced relaxation (indicator of iNOS activity) in IL-1β incubated vessels. Pretreating the vessels with N^ω-nitro-L-arginine (10^(-4) M) did not significantly inhibit the phenylephrine-induced oscillation in IL-1β incubated vessels suggesting a non-iNOS mechanism involved in inducing oscillation. The oscillation frequency and magnitude were significantly inhibited by both dexamethasone and U-74006F. Dexamethasone incubation inhibited L-arginine-induced relaxation and augmented phenylephrine-induced contraction when compared to IL-1β incubated vessels which was not observed in U-74006F incubated vessels. Conclusions: U-74006F may have a therapeutic advantage over dexamethasone in that U-74006F could inhibit pathological oscillation activity with minor effects on L-arginine induced relaxation, and contractile responses to phenylephrine.

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