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

Abstract

Background & Aims: 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 × 10 −6 mol/L), 5-HT (10 −9 to 3 × 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] 5Tyr[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) 5Tyr(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. GASTROENTEROLOGY 2000;118:765-771