Effects of adenosine triphosphate on pulmonary circulation in chronic obstructive pulmonary disease. ATP: a pulmonary vasoregulator?

Abstract

Extracellular adenosine triphosphate (ATP) has potent systemic vasodilator and endothelial-dependent relaxant effects on precontracted vessels. Pulmonary uptake and metabolism of ATP have been described, but experimental effects on pulmonary vessels remain controversial in animals. The effects of an intravenously administered infusion of ATP on pulmonary hemodynamic and gasometric data were assessed in 18 patients with stable chronic obstructive pulmonary disease (COPD). Low doses of ATP (successive rates, 1 and 2 mumol/kg body weight, each for 20 min) were infused in pulmonary hypertensive (H; n = 6) and nonhypertensive (N; n = 6) patients. They were compared with a control group (C; n = 6) that received only solvent, using ANOVA. During ATP infusion, a significant pulmonary vasodilation was demonstrated as simultaneous decreases reached, respectively, -14.2% (Group H; p less than 0.005) and -13.8% (Group N; p less than 0.001) for mean pulmonary artery pressure (Ppa), and -31.7% (H; p less than 0.05) and -20.7% (N; p less than 0.01) for pulmonary vascular resistances (PVR), associated with some worsening of hypoxemia: -6.9% (H; p less than 0.01) and -11.8% (n; p less than 0.005). After ATP withdrawal, significant rebound of these data (above baseline values) reached +10.9% (H; p less than 0.05) and +4.4% (N; p less than 0.05) for Ppa and +24.9% (H; p less than 0.05) and +10.2% (N; p = NS) for PVR. At the low infusion rate used, ATP appeared to be a well-tolerated, short-acting, selective pulmonary vasolidating compound in patients with COPD, but therapeutic use remains premature.