title: Chronic inhibition of nitric oxide ameliorates splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension.
abstract: BACKGROUND
  Vasopressin given during hemorrhage is less effective than when given during a stable state in experimental portal hypertension or patients with cirrhosis (the so-called hyposensitivity phenomenon). This study investigated whether chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor, could potentiate the portal-hypotensive effect of glypressin (a long-acting vasopressin analogue) in portal-hypertensive rats during acute bleeding status.
  
  
  METHODS
  Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (approximately 25 mg/kg/day in tap water) or placebo (tap water) treatment orally from 2 days prior to until 14 days after the operation. At the end of treatment, L-NAME-and placebo-treated PVL rats were subdivided into without-bleeding and with-bleeding groups to assess the effects of glypressin (0.07 mg/kg) on systemic and portal hemodynamics. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin.
  
  
  RESULTS
  As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P < 0.001) without modulating portal pressure (P > 0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P < 0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P < 0.05).
  
  
  CONCLUSIONS
  Chronic inhibition of NO alleviates the splanchnic hyposensitivity to glypressin observed in bleeding PVL rats, suggesting the pathophysiological role of nitric oxide in mediating this splanchnic hyposensitivity.
authors.affiliation: Dept of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taiwan.
authors.forename: H C
authors.initials: HC
authors.lastname: Huang
authors.forename: C J
authors.initials: CJ
authors.lastname: Chu
authors.forename: F Y
authors.initials: FY
authors.lastname: Lee
authors.forename: F Y
authors.initials: FY
authors.lastname: Chang
authors.forename: S S
authors.initials: SS
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: M C
authors.initials: MC
authors.lastname: Hou
authors.forename: C C
authors.initials: CC
authors.lastname: Chan
authors.forename: S L
authors.initials: SL
authors.lastname: Wu
authors.forename: C T
authors.initials: CT
authors.lastname: Chen
authors.forename: S D
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001803:Blood Transfusion; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000628:therapy*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D008236:Lypressin; D000077585:Terlipressin; D019331:NG-Nitroarginine Methyl Ester