ADRENOMEDULLIN INCREASES PULMONARY BLOOD-FLOW IN FETAL SHEEP

We studied the effects of exogenously administered adrenomedullin on f etal pulmonary arterial blood flow in near-term fetal sheep. The hemod ynamic effects of a single injection of adrenomedullin into the left p ulmonary artery were compared with those of acetylcholine; the effects of repeated injections of adrenomedullin were also studied, In seven unanesthetized fetal sheep, catheters were inserted into the left pulm onary artery to administer drugs, and into the main pulmonary and caro tid arteries to measure pressures. An ultrasonic flow transducer was p laced around the left pulmonary artery to measure flow continuously. A single 5-mu g injection of adrenomedullin (1.90 +/- 0.35 mu g/kg of f etal weight) increased pulmonary arterial blood flow significantly, fr om 17 +/- 10 to 120 +/- 21 mL/min (p < 0.001). Two micrograms of acety lcholine (0.74 +/- 0.14 mu g/kg of fetal weight) also increased left p ulmonary arterial blood flow, from 18 +/- 16 to 113 +/- 37 mL/min, but the effect of adrenomedullin on flow was more prolonged than was that of acetylcholine. Additionally, adrenomedullin and acetylcholine simi larly decreased mean pulmonary arterial pressure by 11 and 16%, respec tively, but adrenomedullin did not decrease mean carotid arterial pres sure to the same degree as acetylcholine (2 versus 19%, respectively). Five sequentially repeated injections of adrenomedullin, once every 5 min, increased left pulmonary arterial blood flow significantly in a stepwise manner without significantly changing heart rate or mean pulm onary and carotid arterial pressures. We conclude that exogenously adm inistered adrenomedullin is a pulmonary vasodilator in fetal sheep and has the ability to increase pulmonary blood flow significantly; there is less effect on the systemic circulation. This finding might be imp ortant in considering the therapeutic use of this peptide in the manag ement of persistent pulmonary hypertension in the perinatal period.