Inhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis

doi:10.1016/0270-9139(95)90147-7

Hepatology

Volume 22, Issue 5, November 1995, Pages 1423-1429

https://doi.org/10.1016/0270-9139(95)90147-7 Get rights and content

Abstract

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.

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Citation Excerpt :
These hemodynamic alterations participate in the pathophysiology of portal hypertension which is responsible for the complications of cirrhosis: ascites, hepatorenal syndrome, esophageal varices, encephalopathy. Vasodilatation is present mainly in the mesenteric circulation of cirrhotic patients [2], while peripheral vasodilatation is still debated [3–9]. The alterations of peripheral circulation have been studied with different techniques giving different results.
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Thus, it is conceivable that the vasodilation developing in advanced cirrhosis also involves the muscle districts: a statistically significant inverse correlation between femoral artery blood flow indicized by muscle mass and PVRi was found in patients, but not in healthy control subjects. This is in line with what was reported in conscious cirrhotic rats without ascites and hyperdynamic circulatory syndrome [41], and fully support data provided by the evaluation of forearm blood flow of cirrhotic patients by venous occlusion plethysmography [7–10]. Indeed, it should be pointed out that such a technique expresses the results of flow corrected for the amount of tissue, and, in this respect, provides an assessment that mimic what we performed in the present study.
Muscle wasting likely influences blood flow to muscle districts in advanced cirrhosis. Thus, we assessed systemic hemodynamics and femoral artery blood flow corrected by muscle mass of the lower limb in 13 patients (Child-Pugh classes B and C) and 11 healthy controls.
Systemic hemodynamics were assessed by transthoracic electrical bioimpedance, femoral artery blood flow by duplex-Doppler and muscle mass by magnetic resonance imaging.
As expected, patients exhibited increased cardiac index and reduced peripheral vascular resistance. Femoral artery blood flow did not differ between patients and controls. However, when this parameter was indicized by the muscle mass of the lower limb, which was reduced in patients (median: 3391; range: [2546–4793] vs 5118 [3562–7077] cm³, p = 0.0006), it proved almost doubled in patients (91.1 [59.9–119.4] vs 50.5 [38.6–69.8] μl/min cm³; p = 0.0001). Patient femoral blood flow indicized by muscle mass correlated inversely with peripheral vascular resistance (r = −0.65; p = 0.017) and directly with cardiac index (r = 0.57; p = 0.042).
Vasodilation of muscle districts contributes to the reduced peripheral vascular resistance in advanced cirrhosis. Our findings provide a stronger rationale for the use of non-selective vasoconstrictors to treat hemodynamic-dependent complications of cirrhosis, such as hepatorenal syndrome.
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^☆: This work was supported by a grant from La delegation a la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris (CRC 930202).

^☆☆: Partial results from this study have been already published as an abstract at the 3rd International Meeting on “Biology of Nitric Oxide” in Cologne, Germany, October 1993 (Endothelium 1993;1: S89).

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Other clinical studyInhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis☆,☆☆

Abstract

Am J Med

Gastroenterology

Biochem Biophys Res Commun

Gastroenterology

Gastroenterology

Chest

Chest

Hepatology

The cardiac output at rest in Laennec's cirrhosis

J Clin Invest

Circulatory changes in chronic liver disease

Am J Med

Reduced vascular sensitivity to norepinephrine in portal hypertensive rats

Am J Physiol

Humoral factors may mediate increased rat hindquarter blood flow in portal hypertension

Am J Physiol

Hyperglucagonemia and hyperkinetic circulation after portocaval shunt in the rat

Am J Physiol

Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

Nature

Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide

Other clinical study
Inhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis☆,☆☆