Adrenomedullin (AM), a peptide recently isolated from human blood and pheochromocytoma tissue, has been shown to reduce pulmonary vascular resistance in perfused lungs of cats and rats, pretreated with vasoconstrictors. The effect was not influenced by prostaglandin or nitric oxide inhibitors. We assessed the effect of AM on the pulmonary circulation in 8 chronically instrumented fetal lambs (gest. age 128-135 d). Fetal blood gases and pH were within the normal range. We recorded heart rate, systemic(SAP) and pulmonary (PAP) arterial blood pressures, and left pulmonary arterial blood flow (LPAQ) continuously. Acetylcholine (ACh), 2 μg, or AM, 5 μg boluses, were injected into the superior vena cava or LPA. Both ACh and AM increased LPAQ to a similar extent (Table), but whereas mean SAP and PAP fell significantly with ACh, they fell insignificantly with AM. With ACh, LPAQ returned to baseline within 30 sec, even with repeated boluses. However, AM had a more prolonged effect, increasing with repeated injections. The effects of both ACh and AM were almost completely abolished after N-nitro-L-arginine administration. AM is thus a potent pulmonary vasodilator in the fetus, with a prolonged effect after repeated bolus injections. Its effect is largely mediated by nitric oxide mechanisms.

Table 1
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