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Received for publication March 3, 2003.
Revised March 28, 2003.
Accepted for publication May 8, 2003.
In pulmonary hypertension, systemic infusion of adrenomedullin (ADM), a potent vasodilator peptide, leads to pulmonary vasodilatation. However, systemic blood pressure declines alike. The present study investigated the effect of aerosolized ADM on pulmonary arterial pressure in surfactant depleted newborn piglets with pulmonary hypertension. Animals randomly received aerosolized ADM (ADM, n=6), aerosolized ADM combined with intravenous application of NG-nitro-L-arginine methylester to inhibit nitric oxide synthases (ADM+L- NAME, n=5), or aerosolized normal saline solution (control, n=6). Aerosol therapy was performed in 30 minute intervals for 5 hours. After a total experimental period of 8 hours, mRNA expression of NO synthases (eNOS and iNOS) and endothelin-1 (ET-1) in lung tissue was quantified using TaqMan real time PCR. Aerosolized ADM reduced mean pulmonary artery pressure (MPAP) compared to control (p<0.001; at the end of the study: delta-MPAP - 13.5 ± 1.4 vs. -6.2 ± 2.4 mmHg). PaO2 significantly increased in the ADM (delta PaO2: 243.3 mmHg) and the ADM+L-NAME group (delta PaO2: 217.4 mmHg) compared to the control group (delta PaO2: 82.9 mmHg; p<0.001). Aerosolized ADM did not influence mean systemic arterial pressure (baseline 63.2 ± 2.7 vs. end of the study 66.3 ± 6.5 mmHg, n.s.). NO-synthases gene expressions were 20-30% lower with ADM compared to control. ET-1 gene expression was significantly reduced (>50%) after ADM aerosol therapy (p<0.001). Aerosolized adrenomedullin significantly reduced MPAP without lowering the systemic arterial pressure and improved profoundly the arterial oxygen tension. This effect seems to be mediated at least in part by the reduction of ET-1.
Key words:
ARDS, adrenomedullin, aerosol, endothelin, pulmonary hypertension, vasodilator
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