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l ‐Arginine and arginine analogues: effects on isolated blood vessels and cultured endothelial cells
Author(s) -
Schmidt Harald H.H.W.,
Baeblich Sören E.,
Zernikow Bettina C.,
Klein Marcus M.,
Böhme Eycke
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12104.x
Subject(s) - endothelium , arginine , omega n methylarginine , endothelial stem cell , nitric oxide , citrulline , biochemistry , extracellular , contraction (grammar) , acetylcholine , chemistry , nitrite , biology , endocrinology , medicine , in vitro , amino acid , organic chemistry , nitrate
1 The present study examined effects of arginine (Arg) and various Arg analogues on the vascular tone of rabbit and rat aortic rings, the release of nitrite from cultured bovine aortic endothelial cells and the metabolism of l ‐Arg in bovine and porcine endothelial cell homogenates. The respective d ‐enantiomers or N‐α‐benzoyl‐ l ‐arginine ethyl ester did not substitute for l ‐Arg. 2 In bovine aortic endothelial cells, the release of nitrite was only observed in the presence of l ‐Arg or l ‐Arg methyl ester in the cell culture medium. 3 In dialyzed homogenates of porcine and bovine aortic endothelial cells, l ‐Arg was metabolized independently of NADPH and Ca 2+ to yield l ‐ornithine ( l ‐Orn) and l ‐citrulline ( l ‐Cit). No concomitant nitrite formation was detected. 4 Pretreatment of rabbit and rat aortic rings with l ‐canavanine ( l ‐Can) or N G ‐monomethyl‐ l ‐Arg ( l ‐NMMA) inhibited ATP‐ and acetylcholine‐induced relaxations (endothelium‐dependent) but not glyceryltrinitrate‐induced relaxations (endothelium‐independent). 5 In rabbit aortic rings, Arg and monomeric Arg analogues induced endothelium‐independent relaxations. l ‐Arg methyl ester induced an endothelium‐independent contraction, and l ‐NMMA induced a relaxation in the absence of endothelium and a contraction in the presence of endothelium. Polymeric basic amino acids such as poly l ‐Arg induced endothelium‐dependent relaxations (inhibited by l ‐Can), a subsequent refractoriness to endothelium‐dependent vasodilatators (not prevented by l ‐Can) and endothelial cell death. 6 We suggest that extracellular l ‐Arg is essential for the formation of endothelium‐derived nitrogen oxides (EDNO). However, Arg and Arg analogues do not exert endothelium‐dependent relaxation. l ‐Can and l ‐NMMA inhibit endothelium‐dependent relaxation, consistent with an inhibition of EDNO formation from l ‐Arg, but also exert endothelium‐independent effects on vascular tone.