Effects of nitric oxide inhibition on basal forearm blood flow in patients with nonischemic chronic heart failure.

Abstract

Increased peripheral vascular tone in patients with chronic heart failure (CHF) is an important factor which contributes to increased cardiac afterload and reduced exercise capacity, and consequent further deterioration in CHF. The role of endogenous nitric oxide (NO) in the regulation of basal vascular tone in CHF is controversial. This study has investigated (1) whether basal NO bioavailability is reduced in the peripheral vasculature of patients with nonischemic CHF in the absence of confounding factors influencing endothelial function, and (2) if a difference is found, what clinical characteristics are related to the decreased NO-dependent vasodilation. Basal forearm blood flow (FBF) of 12 patients with CHF and 14 healthy volunteers was measured before and after administration of N(G)-monomethyl-L-arginine (L-NMMA) by venous occlusion plethysmography. After L-NMMA administration, basal FBF in both healthy subjects and patients with CHF decreased significantly, with the decrease in CHF patients being less than that in healthy volunteers (-0.7+/-0.2 vs -1.5+/-0.2 ml/min per 100 ml tissue, P < 0.01). When both groups were considered together, basal FBF was closely related to the decrease in FBF after L-NMMA administration (r = -0.83. P < 0.001). When CHF patients were divided into two groups according to NYHA class, the L-NMMA-induced decrease in FBF in moderate CHF (NYHA III; n = 7) was significantly less than that in mild CHF (NYHA II; n = 5) (-0.36+/-0.13 vs -1.16+/-0.72 ml/min per 100 ml tissue, P < 0.05). In conclusion, basal bioavailability of NO in the peripheral vascular bed in nonischemic CHF is impaired, with an increase in basal vascular tone and with progression of this disorder. This suggests that impaired basal NO bioactivity may make an important contribution to the elevated peripheral vascular tone and expression of symptoms seen in CHF.