Selective alteration of agonist-mediated contraction in hepatic arteries isolated from patients with cirrhosis.
OBJECTIVE
Impaired pressor function in cirrhosis may be specific to certain agonists and vascular territories. This investigation determined whether responses to arginine vasopressin (AVP) and 5-hydroxytryptamine (5-HT) were impaired in hepatic arteries from cirrhotic patients.


METHODS
Cumulative concentration-response curves were produced for AVP (10(-11) to 3 x 10(-6) mol/L), 5-HT (10(-9) to 3 x 10(-5) mol/L), and potassium chloride (2.5 -120 mmol/L) in hepatic arteries from liver donors (noncirrhotic) and recipients (cirrhotic). The receptor stimulated by AVP was identified using a V(1)-receptor antagonist (d[CH(2)](5)Tyr[Me]AVP) and a selective V(2)-receptor agonist (desmopressin [DDAVP]).


RESULTS
Cirrhotic patients had a high heart rate (98 +/- 4 beats/min) and cardiac output (9.87 +/- 0.51 L/min) but low peripheral vascular resistance (711 +/- 35 dyn. s/cm(5)). None of the arteries had a functional endothelium. Maximal contraction (but not sensitivity) to AVP was smaller (P = 0.0002) in hepatic arteries from recipients (34.03% +/- 3.42% KCl) than donors (60.69% +/- 5.56% KCl). 5-HT-mediated contraction was enhanced in recipient hepatic arteries (88.81% +/- 5.43% KCl vs. 71.63% +/- 4. 46% KCl; P = 0.01), but sensitivities were similar (P = 0.20). KCl-mediated contractions were similar (P = 0.87) in both groups. Arteries did not respond to DDAVP, but d(CH(2))(5)Tyr(Me)AVP produced a concentration-dependent rightward shift in the response to AVP.


CONCLUSIONS
These results demonstrate a selective impairment of V(1) receptor-mediated contraction in denuded hepatic arteries from cirrhotic patients, suggesting an abnormality within the vascular smooth muscle.
Islam
M Z
MZ
Liver Research Unit, Department of Medicine, University of Edinburgh, Edinburgh, Scotland.
Williams
B C
BC
Madhavan
K K
KK
Hayes
P C
PC
Hadoke
P W
PW
D001127:Arginine Vasopressin / Q000494:pharmacology*; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D012701:Serotonin