RELAXANT EFFECTS OF L-CITRULLINE IN RABBIT VASCULAR SMOOTH-MUSCLE

1 Vascular endothelium plays a pivotal role in the control of vascular tone through the release of vasoactive factors such as EDRF (NO). 2 T he aim of this study was to investigate whether the addition of exogen ous L-citrulline, the byproduct of the NO-synthesis, could relax vascu lar smooth muscle. 3 L-citrulline relaxed both endothelium-denuded and endothelium-intact rabbit aortic rings precontracted with noradrenali ne 10(-6) M (maximum relaxations induced by L-citrulline 10(-8) M were 74.1 +/- 5.2% vs 51.3 +/- 2.8% in endothelium-denuded and endothelium -intact arteries, respectively). 4 This relaxant effect was enhanced b y zaprinast (a phosphodiesterase type 5 inhibitor) and inhibited by MS -142-1 (a particulate guanylate cyclase inhibitor) and by apamin (a K- Ca-channel blocker). 5 L-citrulline (10(-13)-10(-8) M) increased cGMP levels in aortic rings (maximum value with L-citrulline 10(-8) M was 0 .165 +/- 0.010 pmol cGMP mg(-1) of tissue vs 0.038 +/- 0.009 pmol mg(- 1) of tissue in basal). 6 L-citrulline as well as NO were released fro m endothelial cells in culture stimulated with ACh. The values were 6. 50 +/- 0.50 mu M vs 2.30 +/- 0.20 mu M (stimulated with ACh and basal respectively) for I-citrulline and 4.22+/-0.10 mu M vs 0.87+/-0.26 mu M (stimulated with ACh and basal respectively) for NO. 7 These results suggest that L-citrulline could be released together with NO from end othelium and may have actions complementary to those of NO in the cont rol of vascular smooth muscle relaxation.