Effects of norepinephrine and acetylcholine on portal-systemic collaterals of common bile duct-ligated cirrhotic rat.
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.
Chan
Che-Chang
CC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Chang
Ching-Chih
CC
Huang
Hui-Chun
HC
Wang
Sun-Sang
SS
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Tai
Chun-Ching
CC
Lee
Shou-Dong
SD
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*
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