Selective alteration of agonist-mediated contraction in hepatic arteries isolated from patients with cirrhosis

Background & Aims: Impaired presser function in cirrhosis may be specific t o certain agonists and vascular territories. This investigation determined whether responses to arginine vasopressin (AVP) and 5-hydroxytryptamine (5- MT) were impaired in hepatic arteries from cirrhotic patients. Methods: Cum ulative 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 r ecipients (cirrhotic), The receptor stimulated by AVP was identified using a V-1-receptor antagonist (d[CH2](5)Tyr[Me]AVP) and a selective V-2-recepto r agonist (desmopressin [DDAVP]), Results: Cirrhotic patients had a high he art 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 sensiti vity) to AVP was smaller (P = 0.0002) in hepatic arteries from recipients ( 34.03% +/- 3.42% KCl) than donors (60.69% +/- 5.56% KCI), 5-HT-mediated con traction was enhanced in recipient hepatic arteries (88.81% +/- 5.43% KCI v s, 71.63% +/- 4.46% KCl; P = 0.01), but sensitivities were similar (P = 0.2 0), KCl-mediated contractions were similar (P = 0.87) in both groups. Arter ies did not respond to DDAVP, but d(CH2)(5)Tyr(Me)AVP produced a concentrat ion-dependent rightward shift in the response to AVP, Conclusions: These re sults demonstrate a selective impairment of V-1 receptor-mediated contracti on in denuded hepatic arteries from cirrhotic patients, suggesting an abnor mality within the vascular smooth muscle.