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期刊名称: British Journal of Pharmacology
Volume:128(7)     1999

作者 : Trina K Jeffery ;   Janet C Wanstall ;  
发表期刊 : British Journal of Pharmacology
ISSN : 0007-1188;
出版时间 : 1999
卷期 : 128(7)
起始页码 : 1407
终止页码 : 1418
摘要 : Hypoxic pulmonary hypertension in rats (10% O2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined.Perindopril (30?mg?kg?1?d?1) caused an 18% reduction in pulmonary artery pressure in hypoxic rats.Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries <50?μm o.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30–100 and 101–500?μm o.d.). Perindopril 10 and 30?mg?kg?1?d?1attenuated remodelling in vessels ?100?μm (lungs and histology), 30?mg?kg?1?d?1was effective in vessels 101–500?μm but neither dose prevented hypertrophy of main pulmonary artery. 3?mg?kg?1?d?1was without effect.Perindopril (30?mg?kg?1?d?1) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats.We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.


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