title: Overproduction of nitric oxide inhibits vascular reactivity in portal hypertensive rats.
abstract: OBJECTIVE
  To evaluate the relationship between nitric oxide (NO) and hyperdynamic circulatory status in portal hypertension.
  
  
  METHODS
  Twenty male Sprague Dawley rats (weighing 200 ± 20 g) were randomized into two groups: portal hypertension group (n = 12) and sham-operated control group (n = 8). The portal hypertensive model was established by means of graded constriction of the portal vein. The concentrations of nitrite (NO2 (-)) in the portal vein and peripheral blood were measured by fluorometric assay to reflect NO levels. The reactivity of isolated abdominal aortic rings from rats with partial portal vein constriction and controls was determined by assessing response to administration of potassium chloride (KCl) (10-80 mmol/L) and phenylephrine (10(-9)-10(-4) mol/L) with or without preincubation with NO synthase inhibitor Nω-nitro-L-arginine (L-NNA).
  
  
  RESULTS
  Serum concentrations of NO2 (-) in the portal vein blood (0.766 ± 0.097 μmol/L) and peripheral blood (0.687 ± 0.092 μmol/L) were elevated in portal hypertensive rats, as compared with the concentrations in controls (0.613 ± 0.084 μmol/L and 0.591 ± 0.045 μmol/L respectively, both P < 0.01). In addition, the rates of NO2 (-) in portal vein blood were markedly higher than those in peripheral blood (P < 0.05) in the portal hypertensive rats. Abdominal aortic rings from rats with portal vein constriction exhibited significantly impaired contractility to phenylephrine and KCl, as compared with the control rats. The EC50 values of KCl were markedly higher in the portal hypertensive rings (26.5 ± 0.9 mmol/L) than in the control rings (22.3 ± 1.7 mmol/L, P < 0.01), as were the EC50 values of phenylephrine (37.2 ± 0.4 nmol/L vs control rings: 28.1 ± 0.2 nmol/L, P < 0.01). After preincubation of rings with L-NNA, the difference in EC50 values between portal hypertensive and control rings was no longer statistically significant for either KCl (20.18 ± 0.8 mmol/L vs 19.4 ± 1.2 mmol/L, P > 0.05) or phenylephrine (22.4 ± 1.8 nmol/L vs 21.8 ± 1.4 nmol/L, P > 0.05). However, the maximal concentrations of KCl and phenylephrine for inducing contractions were still significantly lower in the portal hypertensive rings (1.08 ± 0.1 g and 1.43 ± 0.14 g) than in the control rings (1.21 ± 0.11 g and 1.72 ± 0.11 g respectively, both P < 0.05). Thus, addition of the NO synthase inhibitor L-NNA could partially restore contractile responses to KCl and phenylephrine in portal hypertensive rings.
  
  
  CONCLUSIONS
  NO overproduction inhibits the vascular reactivity to vasoconstrictors, and it might be one of the main causes of vasodilatation and hyperdynamic circulatory status in portal hypertension.
authors.affiliation: Xi-Ru Li, Jin-Sheng Wu, Ze-Sheng He, Qing-Jiu Ma, De-Ming Gao, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: X R
authors.initials: XR
authors.lastname: Li
authors.affiliation: Xi-Ru Li, Jin-Sheng Wu, Ze-Sheng He, Qing-Jiu Ma, De-Ming Gao, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: J S
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Xi-Ru Li, Jin-Sheng Wu, Ze-Sheng He, Qing-Jiu Ma, De-Ming Gao, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: Z S
authors.initials: ZS
authors.lastname: He
authors.affiliation: Xi-Ru Li, Jin-Sheng Wu, Ze-Sheng He, Qing-Jiu Ma, De-Ming Gao, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Ma
authors.affiliation: Xi-Ru Li, Jin-Sheng Wu, Ze-Sheng He, Qing-Jiu Ma, De-Ming Gao, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: D M
authors.initials: DM
authors.lastname: Gao
keywords: Hyperdynamic circulatory status; Nitric oxide; Portal hypertension; Vascular reactivity; Vasodilatation