title: Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide.
abstract: BACKGROUND
  It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO.
  
  
  METHODS
  Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization.
  
  
  RESULTS
  Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05).
  
  
  CONCLUSIONS
  Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.
authors.affiliation: Dept. of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taiwan.
authors.forename: C J
authors.initials: CJ
authors.lastname: Chu
authors.forename: F Y
authors.initials: FY
authors.lastname: Lee
authors.forename: S S
authors.initials: SS
authors.lastname: Wang
authors.forename: F Y
authors.initials: FY
authors.lastname: Chang
authors.forename: Y T
authors.initials: YT
authors.lastname: Tsai
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: M C
authors.initials: MC
authors.lastname: Hou
authors.forename: S L
authors.initials: SL
authors.lastname: Wu
authors.forename: C C
authors.initials: CC
authors.lastname: Tai
authors.forename: S D
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003124:Colorimetry; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood*; D011168:Portal System / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013373:Substance P / Q000096:biosynthesis / Q000097:blood*
chemical_list: D009569:Nitric Oxide; D013373:Substance P