Adenosine triphosphate (ATP) treatment of hypoxic pulmonary hypertension (HPH): Comparison of dose dependence in pulmonary and renal circulations

Abstract

In this study we investigated the relationship between pulmonary and renal responses to a low dose infusion of adenosine triphosphate-magnesium chloride (ATP-MgCl 2) in a newborn piglet model of hypoxic pulmonary hypertension (HPH). Three- to five-day-old piglets were cannulated for the measurement of pulmonary and systemic arterial pressure, pulmonary and renal artery flow, and urine output. The animals were then made hypoxic by ventilation with a mixture containing 10% oxygen, 4% CO 2, and balance nitrogen. Serial infusions of ATP-MgCl 2 at 0.01, 0.025, 0.05, 0.1, 0.5, and 1.0 mg/kg/min were compared to preinfusion hypoxia baselines. Hypoxia alone produced a significant elevation in pulmonary artery pressure (73%) and a reduction in pO 2. All dose rates of ATP-MgCl 2 ⩾ 0.05 mg/kg/min produced a significant decrease in mean pulmonary artery pressure. However, as baseline mean pulmonary artery pressure increased there was an increased sensitivity to ATP-induced vasodilation. Pulmonary artery flow did not change during ATP infusion, thus, the change in pulmonary vascular resistance accounted for the decrease in pulmonary artery pressure. In contrast to the response of the pulmonary vasculature, systemic pressure was significantly decreased only during the 1.0 mg/kg/min infusion. Renal blood flow decreased by 46% during hypoxia and decreased further only during the highest dose rate of ATP infused (i.e., 1.0 mg/kg/min). Creatinine clearance (Ccr) and fractional reabsorption of Na (FreNa) also fell during hypoxia, but were not further altered during all but the highest dose of ATP infused. These data suggest that a low dose infusion of ATP-MgCl 2 could decrease the vasoconstriction associated with HPH without concomitant adverse systemic or renal side effects.