L-citrulline mediated relaxation in the control and lipopolysaccharide-treated rat aortic rings.
The present study was undertaken to investigate relaxant effect of L-citrulline in phenylephrine precontracted endothelium intact thoracic aortic rings obtained from control or lipopolysaccharide (1 mg/kg)-treated rats. L-citrulline produced 40+/-3% (n=36) and 60+/-5% (n=24) relaxations in control and lipopolysaccharide-treated rings, respectively. Nitric oxide (NO) release and cyclic guanosine-3',5'-monophosphate levels from the rings were also increased following treatment with L-citrulline. Inhibition of guanylate cyclase, L-citrulline recycling to L-arginine or denudation of the endothelium, significantly reduced L-citrulline-induced relaxations both in control and lipopolysaccharide-treated rings. Treatment of rings with protein synthesis inhibitors prevented relaxations to L-citrulline. Inhibitor of Ca2+-activated K+ channels, tetrabutylammonium or precontraction of the rings with KCl (80 mM), significantly attenuated L-citrulline mediated relaxations in control and lipopolysaccharide-treated rings. Thus, L-citrulline seems to exert significant relaxation by supplementing the release of NO due to its recycling to L-arginine, which gets further augmented after lipopolysaccharide treatment.
Raghavan
S A
SA
Division of Pharmacology, Central Drug Research Institute, Post Box 173, -226001, Lucknow, India.
Dikshit
M
M
D000818:Animals; D001011:Aorta; D001120:Arginine / Q000494:pharmacology; D002956:Citrulline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D006146:Guanidines; D008070:Lipopolysaccharides; D009573:Nitrites; D015221:Potassium Channels; D005973:Glutamine; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D003513:Cycloheximide; D006152:Cyclic GMP; C004479:pimagedine; D003345:Corticosterone