Role of the endothelium on vasoactive agents in patients with liver cirrhosis

Background and Aim:  Patients with liver cirrhosis exhibit peripheral vasodilatation and decreased vasoconstrictor responsiveness. We investigated the role of the endothelium in these patients. Methods:  Nine patients with cirrhosis and seven controls were recruited. Responses to acetylcholine, bradykinin and sodium nitroprusside were obtained using forearm plethysmography. Responses to norepinephrine (100 ng/min) were obtained in the absence and combined presence of the cyclo‐oxygenase inhibitor, indomethacin, and the nitric oxide (NO) synthase inhibitor, N G ‐monomethyl‐L‐arginine. Results:  Responses to acetylcholine (area under curve: controls vs cirrhotic, 10326 ± 1400 vs 18490 ± 2787 units; P  = 0.036), but not to bradykinin (15619 ± 3557 vs 12415 ± 3823 units) or sodium nitroprusside, were significantly higher in patients with cirrhosis. Responses to norepinephrine were significantly dampened in cirrhotics (percentage increase in forearm blood flow; controls vs cirrhotics, −50.50 ± 2.69 vs −26.39 ± 5.44; P  = 0.036) but this blunted response was no longer apparent following the administration of both blockers. Conclusions:  We conclude that: (i) there is an increased response to acetylcholine but not to bradykinin; and (ii) that an enhanced production of prostacyclin and/or NO is responsible for the dampened response to norepinephrine.