title: Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis.
abstract: OBJECTIVE
  To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats.
  
  
  METHODS
  Rat renal arteries from Sham (n= 15), pre-hepatic portal hypertension (PPVL;n= 15) and bile duct ligation and excision-induced cirrhosis (BDL;n= 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10-6-10-3mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10-9-3 × 10-6mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catabolizes ADMA.
  
  
  RESULTS
  In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD2values to ADMA were similar in the Sham and PPVL groups (4.20 ± 0.08 and 4.11 ± 0.09,P> 0.05, respectively), but were lower than those of the BDL group (4.79 ± 0.16,P< 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of pD2and maximal relaxation, among the 3 groups studied. Treatment with ADMA (3 × 10-4mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher (P< 0.05) in the BDL group compared with that for the Sham and PPVL groups. The mRNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased (P< 0.05) in PPVL and further enhanced (P< 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group.
  
  
  CONCLUSIONS
  Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Segarra
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Cortina
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Mauricio
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Novella
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Lluch
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Navarrete-Navarro
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Noguera
authors.affiliation: Gloria Segarra, Belén Cortina, María Dolores Mauricio, Susana Novella, Javier Navarrete-Navarro, Inmaculada Noguera, Pascual Medina, Department of Physiology, University of Valencia and Institute of Health Research INCLIVA, Hospital Clínico Universitario Valencia, 46010 Valencia, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Medina
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood / Q000150:complications / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000201:enzymology; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
keywords: Asymmetric dimethylarginine; Cirrhosis; Dimethylarginine dimethylaminohydrolase; Nitric oxide; Nitric oxide inhibitors; Portal hypertension