Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function

Jeffery, T. K. and Wanstall, J. C. (1999) Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function. British Journal of Pharmacology, 128 7: 1407-1418. doi:10.1038/sj.bjp.0702923


Author Jeffery, T. K.
Wanstall, J. C.
Title Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
Publication date 1999-01-01
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0702923
Volume 128
Issue 7
Start page 1407
End page 1418
Total pages 12
Place of publication United Kingdom
Publisher Nature Publishing group
Collection year 1999
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
730110 Respiratory system and diseases (incl. asthma)
1115 Pharmacology and Pharmaceutical Sciences
Abstract 1 Hypoxic pulmonary hypertension in rats (10% O-2, 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. 2 Perindopril (30 mg kg(-1) d(-1)) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3 Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries (50 mu m 0.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30-100 and 101-500 mu m o.d.). Perindopril 10 and 30 mg kg(-1) d(-1) attenuated remodelling in vessels less than or equal to 100 mu m (lungs and histology), 30 mg kg(-1) d(-1) was effective in vessels 101-500 mu m but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg(-1) d(-1) was without effect. 4 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. 5 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.
Keyword Pharmacology & Pharmacy
Pulmonary Hypertension
Perindopril
Ace Inhibitor
Pulmonary Vascular Remodelling
Pulmonary Vascular Function
Chronic Hypoxia
Pulmonary Artery
Isolated Lungs
Chronically Hypoxic Rats
Artery Preparations
Nitric-oxide
Captopril
Vasoconstriction
Hypertrophy
Reactivity
Expression
Responses
Pressure
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Mon, 20 Aug 2007, 01:53:18 EST