title: Effects of norepinephrine and acetylcholine on portal-systemic collaterals of common bile duct-ligated cirrhotic rat.
abstract: BACKGROUND
  Catecholamine exerts profound vascular effects on vascular smooth muscle, and serum norepinephrine (Nepi) and sympathetic nervous activity are increased in cirrhosis. The vascular response of Nepi and acetylcholine (Ach) in portal-systemic collaterals of cirrhotic rats is unknown. The purpose of the present study was to investigate the effects of Nepi and Ach on portal-systemic collaterals of common bile duct-ligated (BDL) cirrhotic rats.
  
  
  METHODS
  Perfusion studies were performed 6 weeks after BDL when hepatic cirrhosis was induced. Three series of experiments were performed in BDL rats: (i) the Nepi (10(-10) mol/L-10(-5) mol/L) vasoconstrictory responses with (n = 6) and without (n = 5) alpha1- (phentolamine, 5 x 10(-6) mol/L) or beta- (propranolol, 10(-5) mol/L) receptor antagonist (n = 6 and 5, respectively); (ii) the Ach (10(-8) mol/L-10(-5) mol/L) vasodilatory responses in Nepi- preconstricted portal-systemic collaterals in the absence (n = 7) or presence (n = 8) of N(pi)- L-nitro-arginine (NNA, 10(-4) mol/L); and (iii) the effect of indomethacin (10(-5) mol/L; n = 6) on Nepi responses. The collateral vascular responses were evaluated by the in situ collateral perfusion.
  
  
  RESULTS
  Norepinephrine significantly increased the perfusion pressure and was inhibited by phentolamine (P < 0.05). The constrictive responses of Nepi were not significantly modified in the presence of propranolol (P > 0.05). Acetylcholine produced >50% relaxation of the Nepi-preconstricted collateral vessels and was inhibited by NNA (P < 0.05). In addition, indomethacin significantly enhanced the constrictive response of Nepi (P < 0.05).
  
  
  CONCLUSIONS
  Norepinephrine has a vasoconstrictive effect on the portal-systemic collaterals of cirrhotic rats and this effect was mediated by alpha1-receptor. Both nitric oxide and prostaglandin are endogenous modulators in the collateral circulation of cirrhotic rats.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Che-Chang
authors.initials: CC
authors.lastname: Chan
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Full-Young
authors.initials: FY
authors.lastname: Chang
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Tai
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D003097:Collateral Circulation / Q000187:drug effects*; D003135:Common Bile Duct / Q000503:physiopathology / Q000601:surgery; D006975:Hypertension, Portal / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008026:Ligation; D008099:Liver / Q000098:blood supply*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011168:Portal System / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D011433:Propranolol; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin; D010646:Phentolamine