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Circulation Journal
Vol. 66 (2002) No. 7 p. 627-632



Clinical Investigation

Recent studies have demonstrated that proinflammatory cytokines induce large amounts of nitric oxide (NO) and that the amount increases in patients with congestive heart failure (CHF). There are, however, few reports regarding the relationships between NO production, cytokines and the severity of heart failure, so the plasma concentrations of nitrite and nitrate (NOx), tumor necrosis factor-α (TNF-α) and brain natriuretic peptide (BNP) were measured in 43 patients with CHF caused by dilated cardiomyopathy and 26 age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using plethysmography during infusions of acetylcholine and nitroglycerin and after the administration of the NO synthesis inhibitor L-NMMA (NG-monomethyl-L-arginine). Plasma concentrations of both NOx and TNF-α were significantly higher in the patient group than in the control group (p<0.001) and correlated closely with BNP concentrations (p<0.001). There was a positive relationship between NOx and TNF-α concentrations (r=0.80, p<0.001). Administration of L-NMMA significantly reduced FBF in both groups, and the percent change in FBF from baseline correlated significantly with TNF-α concentrations (r=0.63, p<0.001). The FBF response to acetylcholine was depressed in the patient group and correlated inversely with TNF-α concentrations. The FBF response to nitroglycerin did not correlate with TNF-α concentrations. The findings indicate that the concentrations of NO and TNF-α in patients with CHF increase in proportion to the severity of heart failure, and that TNF-α plays a role in the enhanced systemic and local production of NO. (Circ J 2002; 66: 627 - 632)


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