title: Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects.
abstract: BACKGROUND
  Impaired endothelium-dependent NO-mediated vasodilation is a key feature of essential hypertension and may precede the increase in blood pressure. We investigated whether transport of the NO precursor L-arginine is related to decreased endothelial function.
  
  
  RESULTS
  Radiotracer kinetics ([3H]L-arginine) were used to measure forearm and peripheral blood mononuclear cell arginine uptake in hypertensive subjects (n=12) and in 2 groups of healthy volunteers with (n=15) and without (n=15) a family history of hypertension. In conjunction, forearm blood flow responses to acetylcholine and sodium nitroprusside were measured before and after a supplemental intra-arterial infusion of L-arginine. In vivo and in vitro measures of L-arginine transport were substantially reduced in the essential hypertension and positive family history groups compared with the negative family history group; however, no difference was detected in peripheral blood mononuclear cell mRNA or protein expression levels for the cationic amino acid transporter CAT-1. Plasma concentrations of L-arginine and N(G),N(G')-dimethylarginine (ADMA) did not differ between groups. L-arginine supplementation improved the response to acetylcholine only in subjects with essential hypertension and positive family history.
  
  
  CONCLUSIONS
  Similar to their hypertensive counterparts, normotensive individuals at high risk for the development of hypertension are characterized by impaired L-arginine transport, which may represent the link between a defective L-arginine/NO pathway and the onset of essential hypertension. The observed transport defect is not due to apparent alterations in CAT-1 expression or elevated endogenous ADMA.
authors.affiliation: Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, Melbourne, Victoria, Australia.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schlaich
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Parnell
authors.forename: Belinda A
authors.initials: BA
authors.lastname: Ahlers
authors.forename: Samara
authors.initials: S
authors.lastname: Finch
authors.forename: Tanneale
authors.initials: T
authors.lastname: Marshall
authors.forename: Wei-Zheng
authors.initials: WZ
authors.lastname: Zhang
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D001692:Biological Transport; D027201:Cationic Amino Acid Transporter 1 / Q000097:blood / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005542:Forearm; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D027201:Cationic Amino Acid Transporter 1; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine