Numan N A, Gillespie M N, Altiere R J
University of Kentucky, College of Pharmacy, Lexington.
Pulm Pharmacol. 1990;3(1):29-33. doi: 10.1016/0952-0600(90)90006-5.
Pulmonary vascular relaxant effects of the 28-amino acid atrial natriuretic peptide and atriopeptins I, II and III (21, 23 and 24 amino acid peptides, respectively) were studied in isolated blood vessels and in perfused rat lungs. In isolated tissue studies, intrapulmonary arteries were more responsive to the relaxant effects of atrial peptides than the main pulmonary artery or aorta. In perfused lung preparations, each of the four atrial peptides produced dose-dependent pulmonary vasodilation of PGF2 alpha or hypoxia-induced pulmonary vasoconstriction. Atriopeptin I was the least potent pulmonary vasodilator peptide in all studies. Pretreatment of perfused lungs with various peptidase inhibitors, including the angiotensin converting enzyme inhibitors, captopril and MK-521, the carboxypeptidase inhibitor, 1,10-phenanthroline, and the aminopeptidase inhibitor, bestatin, variably potentiated the pulmonary vasodilator activities of the atrial peptides. The results demonstrate that atrial peptides released from the right heart into the pulmonary circulation can have potent vasorelaxant effects in the pulmonary vascular bed and further suggest that upon passage through the lung atrial peptides may undergo metabolic degradation that alters their pulmonary vasodilator activities.
在离体血管和灌注大鼠肺中研究了28个氨基酸的心房利钠肽及心房肽Ⅰ、Ⅱ和Ⅲ（分别为21、23和24个氨基酸的肽）的肺血管舒张作用。在离体组织研究中，肺内动脉对心房肽舒张作用的反应比主肺动脉或主动脉更敏感。在灌注肺制备中，四种心房肽中的每一种均产生剂量依赖性的对PGF2α或缺氧诱导的肺血管收缩的肺血管舒张作用。在所有研究中，心房肽Ⅰ是效力最低的肺血管舒张肽。用各种肽酶抑制剂，包括血管紧张素转换酶抑制剂卡托普利和MK-521、羧肽酶抑制剂1,10-菲咯啉以及氨肽酶抑制剂贝司他汀对灌注肺进行预处理，可不同程度地增强心房肽的肺血管舒张活性。结果表明，从右心释放到肺循环中的心房肽在肺血管床可具有强大的血管舒张作用，并进一步提示，心房肽通过肺时可能经历代谢降解，从而改变其肺血管舒张活性。
