PMID- 2282457 OWN - NLM STAT- MEDLINE DCOM- 19910315 LR - 20190510 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 101 IP - 1 DP - 1990 Sep TI - L-arginine and arginine analogues: effects on isolated blood vessels and cultured endothelial cells. PG - 145-51 AB - 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-alpha-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 Ca2+ 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 NG-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 vasodilators (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. FAU - Schmidt, H H AU - Schmidt HH AD - Institut fur Pharmakologie, Freie Universitat Berlin, F.R.G. FAU - Baeblich, S E AU - Baeblich SE FAU - Zernikow, B C AU - Zernikow BC FAU - Klein, M M AU - Klein MM FAU - Bohme, E AU - Bohme E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Nitrites) RN - 0 (Nitrogen Oxides) RN - 27JT06E6GR (omega-N-Methylarginine) RN - 29VT07BGDA (Citrulline) RN - 94ZLA3W45F (Arginine) RN - 967-88-4 (benzoyl L-arginine methyl ester) RN - E524N2IXA3 (Ornithine) RN - ZTI6C33Q2Q (Guanethidine) SB - IM MH - Animals MH - Arginine/analogs & derivatives/metabolism/*pharmacology MH - Cattle MH - Citrulline/metabolism MH - Endothelium, Vascular/*cytology/drug effects MH - Guanethidine/pharmacology MH - In Vitro Techniques MH - Male MH - Muscle, Smooth, Vascular/*drug effects MH - Nitrites/pharmacology MH - Nitrogen Oxides/metabolism MH - Ornithine/metabolism MH - Rabbits MH - Rats MH - Rats, Inbred Strains MH - Stereoisomerism MH - Swine MH - omega-N-Methylarginine PMC - PMC1917657 EDAT- 1990/09/01 00:00 MHDA- 1990/09/01 00:01 PMCR- 1991/09/01 CRDT- 1990/09/01 00:00 PHST- 1990/09/01 00:00 [pubmed] PHST- 1990/09/01 00:01 [medline] PHST- 1990/09/01 00:00 [entrez] PHST- 1991/09/01 00:00 [pmc-release] AID - 10.1111/j.1476-5381.1990.tb12104.x [doi] PST - ppublish SO - Br J Pharmacol. 1990 Sep;101(1):145-51. doi: 10.1111/j.1476-5381.1990.tb12104.x.