Akademik Veri Yönetim Sistemi
Journal of Investigative Medicine, cilt.44, sa.3, 1996 (Scopus)
Hypoxia decreases vasorelaxation and leads to pulmonary arterial hypertension. A newly identified 52 amino-acid peptide adrenomedullin (ADM) exerts vasodilator effect in the intact animals under normoxic states. We studied the effect of human ADM on rat pulmonary arterial and aortic rings under normoxic and hypoxic conditions. Under normoxia, ADM caused a concentration-dependent relaxation of precontracted aortic and pulmonary arterial rings; the relaxation was much more pronounced in pulmonary than in aortic rings, and was abolished by nitric oxide (NO) synthesis inhibitor L-NAME and by de-endothelialization. A fragment of ADM, ADMi3-52 caused similar relaxation in pulmonary arterial rings, but not in the aortic rings, and the relaxation of pulmonary artery caused by ADMi3-S2 was abolished by L-NAME and by de-endothelialization. During hypoxia, ADM13-52 failed to relax pulmonary arterial rings, but ADM caused modest relaxation of pulmonary arterial rings (one third of the relaxation during normoxia).The ADM-induced pulmonary artery ring relaxation was abolished by pretreatment with indomethacin. This study indicates that vasorelaxant effect of ADM is more pronounced in pulmonary artery than in the systemic artery; ADM has more potent vasodilator effect than ADM13-52; ADM relaxes hypoxic pulmonary artery via indomethacin-sensitive pathway; amino acids 1-12 in ADM must be present for relaxation of chronic hypoxic pulmonary artery rings; and lastly, endothelium/NO is necessary for the ADM-mediated relaxation.