Adenosine is a pulmonary vasodilator in newborn lambs

We investigated the systemic and pulmonary vascular effects of adenosine and determined plasma adenosine levels in pulmonary circulation in 12 newborn lambs during normoxia and during alveolar hypoxia (10% O2, 5% CO2, and 85% N2). Lambs were instrumented at 7 days of age with catheters in the descending aorta, main pulmonary artery, and right and left atria, and a flow transducer around the main pulmonary artery, and were studied following a 3-day recovery. Adenosine or an equal volume of normal saline (control) was infused into the right atrial line in doses ranging from 0.01 to 2.5 mumol/kg/min. In normoxic lambs, adenosine caused a significant decrease in pulmonary vascular resistance and increase in heart rate in doses of 0.15 to 2.5 mumol/kg/min and a decrease in systemic vascular resistance, with increase in cardiac output in doses of 0.3 to 2.5 mumol/kg/min. Baseline plasma adenosine levels in pulmonary artery and left atrium decreased significantly during alveolar hypoxia. Adenosine infusion in hypoxic lambs caused decreases in pulmonary artery pressure and pulmonary vascular resistance at all the doses tested. Aortic pressure and systemic vascular resistance decreased, and heart rate and cardiac output increased at doses greater than or equal to 0.3 mumol/kg/min in hypoxic lambs during adenosine infusion. The pulmonary vascular effects of adenosine in hypoxic lambs were attenuated by prior treatment of animals with aminophylline. Thus, adenosine appears to be an important regulator of pulmonary vascular response to hypoxia in newborn lambs. Its vasodilator effects were specific for pulmonary circulation when it was infused in doses less than or equal to 0.15 mumol/kg/min into the right atrium and appear to be mediated by P1 purinergic receptors.