INDUCIBLE L-ARGININE NITRIC-OXIDE PATHWAY IN HUMAN INTERNAL MAMMARY ARTERY AND SAPHENOUS-VEIN

To characterize the L-arginine/nitric oxide (NO) pathway in human vasc ular smooth muscle (VSM), contractile responses of isolated internal m ammary arteries (IMA) and saphenous veins (SV) were observed after ind uction of NO synthase by interleukin-1 beta (IL-1 beta) or by Lipopoly saccharide (LPS). In IL-1 beta-treated endothelium-denuded rings, cont ractile responses to phenylephrine were reduced in SV rings only. Maxi mum phenylephrine-induced contraction was depressed by similar to 50%. This was not modified by the presence of indomethacin, N-G-nitro-L-ar ginine methyl ester (L-NAME), or methylene blue (MeB). In LPS-treated vessels, contractile responses were depressed in both SV and IMA rings (40%), and this was not affected by indomethacin. In SV, L-NAME, N-G- monomethyl-L-arginine, or MeB did not affect the inhibitory effect of LPS, whereas the effect was reversed in IMA by these inhibitors. In LP S-treated IMA, but not in SV, exogenous L-arginine evoked significant vasodilation (20%). We conclude that VSM of the human IMA possesses an L-arginine/NO pathway inducible by LPS. In SV, LPS or IL-1 beta treat ment inhibits contraction by an unidentified system that is not depend ent on NO synthase or on guanylate cyclase activities.