Brief adrenomedullin inhalation leads to sustained reduction of pulmonary artery pressure.
The effect of aerosolised adrenomedullin (ADM), a potent vasodilator peptide, on pulmonary artery pressure was studied for 24 h in a surfactant-depleted piglet model. Animals received either aerosolised ADM (50 ng.kg(-1).min(-1), ADM, n=6), or aerosolised normal saline solution (control, n=6). Aerosol therapy was performed for a 2 h treatment period followed by a 22 h observation period. Ventilator settings were adapted to keep arterial oxygen tension and carbon dioxide arterial tension between 13.3-14.6 kPa and 4.9-5.7 kPa, respectively. Aerosolised ADM reduced mean pulmonary artery pressure (MPAP) compared with the control group (end-point median 24 h after therapy start: DeltaMPAP -14.0 versus -8.0 mmHg; 23.5 h after therapy start). After therapy start, mean systemic arterial pressure (MAP) was not significantly different between the groups (end-point median: MAP ADM 70 (61/74) versus control 72 (54/81) mmHg). Endothelin-1, a potent pulmonary vasoconstrictor, is regulated by ADM via cAMP. Twenty two hours after inhalation of aerosolised ADM, endothelin-1 mRNA in lung tissue and endothelin-1 protein expression in pulmonary arteries was reduced compared with controls (median semi-quantitative immunhistochemical score: ADM 0.21, control 0.76). Aerosolised adrenomedullin significantly reduced mean pulmonary artery pressure independently of arterial oxygen tension.
Klinik für Kinder und Jugendliche, Loschgestrasse 15, D-91054 Erlangen, Germany. michael.kandler@web.de
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K
von der Hardt
M A
MA
Kandler
M
M
Chada
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A
Cubra
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Schoof
K
K
Amann
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Rascher
J
J
Dötsch
D000280:Administration, Inhalation; D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D023421:Models, Animal; D010100:Oxygen / Q000097:blood; D010455:Peptides / Q000008:administration & dosage*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010455:Peptides; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D053607:Adrenomedullin; D010100:Oxygen