Inhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis.
Increased vascular production of nitric oxide (NO) may contribute to the peripheral vasodilation and hyperdynamic state complicating advanced liver cirrhosis. In this study, we examined the effect on forearm blood flow of local brachial artery infusion of noradrenaline (NA) and NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO-synthase, in 10 alcoholic ascitic cirrhotic patients (patients with decompensated alcohol-induced liver disease: DALD group) and 10 patients with well-compensated alcohol-induced liver disease (CALD group). Forearm blood flow was measured by venous occlusion plethysmography. As compared with the CALD group, the DALD group had higher cardiac index and forearm blood flow as well as lower systemic blood pressure and vascular resistance. Infusions of NA and L-NMMA produced similar reduction in resting blood flow in the CALD group. However, in the DALD group, NA was significantly less effective than L-NMMA. The forearm vasoconstrictor response to NA was also significantly reduced in the DALD group when compared with the CALD group. In the DALD group, NA decreased forearm blood flow by 21.0 +/- 6.2% and increased vascular resistance by 37.2 +/- 12.3%, whereas respective changes in the CALD group were 41.8 +/- 6.2% (P < .01) and 77.8 +/- 9.9% (P < .02). In contrast, L-NMMA induced greater forearm vasoconstriction in the DALD group than in the CALD group. In decompensated patients, L-NMMA decreased forearm blood flow by 50.4 +/- 2.7% and increased vascular resistance by 115.9 +/- 14.4%, whereas changes in compensated patients were 38.2 +/- 4.9% (P < .05) and 77.4 +/- 16.2% (NS), respectively. These results are consistent with the hypothesis that increased vascular synthesis of NO contributes to the high dynamic state of patients with advanced cirrhosis.
Campillo
B
B
Service d'Hépato-gastroentérologie et Réeducation Digestive, Hôpital A. Chenevier, Créteil, France.
Chabrier
P E
PE
Pelle
G
G
Sediame
S
S
Atlan
G
G
Fouet
P
P
Adnot
S
S
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine