The Inhibitory Effect of Ethanol on Interleukin-1 β-Induced Suppression of Contractile Response in the Rat Superior Mesenteric Artery.

Abstract

Interleukin (IL)-1 β is a cytokine that is upregulated by the pro-inflammatory bacterial endotoxin lipopolysaccharide. This study examined the effect of ethanol on IL-1 β-mediated suppression of phenylephrine-induced contractility and inducible nitric oxide synthase (iNOS) expression in the rat superior mesenteric artery (SMA). IL-1 β suppressed the phenylephrine-induced contractile response, and this effect was inhibited by ethanol. The IL-1 β-mediated effects were also blocked by cycloheximide, an inhibitor of protein synthesis, as well as AMT and 1400W, which are iNOS inhibitors, and PTIO, an NO scavenger. However, indomethacin, a cyclooxygenase (COX) inhibitor that promotes NO-independent vasodilation, did not affect IL-1 β-mediated suppression of the contractile response. Western blot analysis revealed that iNOS levels in SMA were upregulated by IL-1 β and inhibited by ethanol (50 and 100 mM). These results indicate that the suppression of the SMA contractile response by IL-1 β requires iNOS activity, but not COX-2. Furthermore, these data suggest that ethanol inhibits the effects of IL-1 β on the contractile response via inhibition of iNOS, rather than COX-2.