title: Selective alteration of agonist-mediated contraction in hepatic arteries isolated from patients with cirrhosis.
abstract: 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.
authors.affiliation: Liver Research Unit, Department of Medicine, University of Edinburgh, Edinburgh, Scotland.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Islam
authors.forename: B C
authors.initials: BC
authors.lastname: Williams
authors.forename: K K
authors.initials: KK
authors.lastname: Madhavan
authors.forename: P C
authors.initials: PC
authors.lastname: Hayes
authors.forename: P W
authors.initials: PW
authors.lastname: Hadoke
mesh_terms: 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*
chemical_list: D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D012701:Serotonin