Mechanisms of a clonidine-induced decrease in portal pressure in normal and cirrhotic conscious rats.
The effects of clonidine on portal pressure and splanchnic blood flow were studied in conscious rats with sinusoidal portal hypertension due to cirrhosis induced by bile duct ligation. In cirrhotic and sham-operated rats, clonidine (20 micrograms per kg body weight, intravenously) significantly reduced portal, pressure from 19.0 +/- 0.6 to 14.5 +/- 1.0 mmHg and from 9.8 +/- 0.9 to 7.3 +/- 0.5 mmHg, respectively. No significant change in systemic hemodynamics was observed. In cirrhotic rats, clonidine reduced portal pressure, probably by producing a significant increase in portal tributary vascular resistance leading to a 25% decrease in portal tributary blood flow (radioactive microsphere method). In sham-operated rats, clonidine reduced portal pressure presumably by decreasing hepatic portal vascular resistance, since no significant change in portal tributary blood flow was observed. In both groups, clonidine administration significantly decreased plasma noradrenaline concentration. Placebo administration produced neither significant hemodynamic nor significant plasma noradrenaline concentration change. These findings indicate that the sympathetic regulation of the splanchnic circulation is impaired in cirrhotic rats.
Roulot
D
D
Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Braillon
A
A
Gaudin
C
C
Ozier
Y
Y
Girod
C
C
Lebrec
D
D
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011169:Portal Vein; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014690:Venous Pressure / Q000187:drug effects
D003000:Clonidine; D009638:Norepinephrine