Effects of cilazapril, a novel angiotensin converting enzyme inhibitor, on the structure of pulmonary arteries of rats exposed to chronic hypoxia.
Chronic hypoxia is known to be associated with a thickening of the media of pulmonary arteries. The goal of the present study was to assess if cilazapril, a novel long-acting angiotensin converting enzyme (ACE) inhibitor, could prevent this thickening. For this purpose, three groups of rats were studied. One group was kept in normal room air. Two other groups were exposed to chronic hypoxia (inspired fraction of oxygen equal to 8% during 4 weeks). One group of hypoxic rats was treated with placebo and the other group received cilazapril (as food admixture of approximately 3 mg/kg/day). After 4 weeks, rats were anesthetized and pulmonary artery pressure and hematocrit measured. Then, the lungs were perfused and fixed and morphometry of the pulmonary arteries was performed. Hypoxia induced an increase in pulmonary artery pressure and hematocrit associated with a dramatic increase in the thickness of the media of the pulmonary arteries. Cilazapril completely prevented the thickening of the media of the pulmonary arteries but did not significantly decrease the pulmonary artery pressure or right ventricular weight.
Clozel
J P
JP
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Saunier
C
C
Hartemann
D
D
Fischli
W
W
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D017315:Cilazapril; D006321:Heart / Q000033:anatomy & histology; D006439:Hemodynamics / Q000187:drug effects; D006984:Hypertrophy / Q000209:etiology / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000033:anatomy & histology / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril