L-Citrulline mediated relaxation in the control and lipopolysaccharide-treated rat aortic rings

The present study was undertaken to investigate relaxant effect of L-citrul line in phenylephrine precontracted endothelium intact thoracic aortic ring s obtained from control or lipopolysaccharide (1 mg/kg)-treated rats. L-Cit rulline produced 40 +/- 3% (n = 36) and 60 +/- 5% (n = 24) relaxations in c ontrol and lipopolysaccharide-treated rings, respectively. Nitric oxide (NO ) release and cyclic guanosine-3',5'-monophosphate levels from the rings we re also increased following treatment with L-Citrulline. Inhibition of guan ylate cyclase, L-citrulline recycling to L-arginine or denudation of the en dothelium, significantly reduced L-citrulline-induced relaxations both in c ontrol and lipopolysaccharide-treated rings. Treatment of rings with protei n synthesis inhibitors prevented relaxations to L-citrulline. Inhibitor of Ca2+-activated K+ channels, tetrabutylammonium or precontraction of the rin gs with KCl (80 mM), significantly attenuated L-citrulline mediated relaxat ions in control and lipopolysaccharide-treated rings. Thus, L-citrulline se ems to exert significant relaxation by supplementing the release of NO due to its recycling to L-arginine, which gets further augmented after lipopoly saccharide treatment. (C) 2001 Elsevier Science B.V. All rights reserved.