Role of the endothelium on vasoactive agents in patients with liver cirrhosis.
OBJECTIVE
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.
Battaglia
Samuel
S
Liver Clinic, Austin and Repatriation Hospital, Melbourne, Victoria, Australia.
Angus
Peter
P
Chin-Dusting
Jaye P F
JP
D000109:Acetylcholine / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010991:Plethysmography; D012720:Severity of Illness Index; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine