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 t he peripheral vasodilation and hyperdynamic state complicating advance d liver cirrhosis, In this study, we examined the effect on forearm bl ood now of local brachial artery infusion of noradrenaline (NA) and NG -monomethyl-L-arginine (L-NMMA), an inhibitor of NO-synthase, in 10 al coholic ascitic cirrhotic patients (patients with decompensated alcoho l-induced liver disease: DALD group) and 10 patients with well-compens ated alcohol-induced liver disease (CALD group). Forearm blood now was measured by venous occlusion plethysmography. As compared with the CA LD group, the DALD group had higher cardiac index and forearm blood no w as well as lower systemic blood pressure and vascular resistance. In fusions of NA and L-NMMA produced similar reduction in resting blood n ow in the CALD group. However, in the DALD group, NA was significantly less effective than L-NMMA. The forearm vasoconstrictor response to N A was also significantly reduced in the DALD group when compared with the CALD group. In the DALD group, NA decreased forearm blood Bow by 2 1.0 +/- 6.2% and increased vascular resistance by 37.2 +/- 12.3%, wher eas 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 forea rm vasoconstriction in the DALD group than in the CALD group. In decom pensated patients, L-NMMA decreased forearm blood flow by 50.4 +/- 2.7 % and increased vascular resistance by 115.9 +/- 14.4%, whereas change s in compensated patients were 38.2 +/- 4.9% (P < .05) and 77.4 +/- 16 .2% (NS), respectively. These results are consistent with the hypothes is that increased vascular synthesis of NO contributes to the high dyn amic state of patients with advanced cirrhosis.