Adrenomedullin is inactivated in the lungs of neonatal piglets

Adrenomedullin, a novel 52 amino acid peptide normally present in adult human plasma, has been shown to induce systemic hypotension in the adult rat, pig and cat, and in the new-born piglet. Little is known about the site (s) of adrenomedullin inactivation in adults or neonates. Groups of five 0-2-day old and 2-week old anaesthetized piglets were prepared to enable continuous monitoring of cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, mean systemic vascular resistance and mean pulmonary vascular resistance. In both age groups, injections of human adrenomedullin1-52 into the left atrium produced significant (P < 0.05) reductions in mean systemic arterial pressure and mean pulmonary artery pressure. Although injections of similar doses of human adrenomedullin1-52 into the right atrium produced significant (P < 0.05) decreases in mean pulmonary artery pressure, there were no appreciable alterations in mean systemic arterial pressure in either age group. These results suggest that the systemic vasodilator properties of human adrenomedullin1-52 are reduced upon first pass through the pulmonary circulation in 2-week old piglets, a phenomenon that is present at birth.