Inhibition of angiotensin-converting enzyme by perindopril diacid in canine oleic acid pulmonary edema.
To test the hypothesis that angiotensin II could be a mediator of acute lung injury, we studied the effects of perindopril diacid, a new angiotensin-converting enzyme inhibitor, on hemodynamics, blood gases, lung mechanics, and extravascular lung water (EVLW). Twenty-four dogs were anesthetized, paralyzed and ventilated with a fraction of inspired oxygen of 0.4 in which pulmonary edema was induced by 0.1 ml/kg iv oleic acid. Perindopril diacid (1 mg/kg) was administered iv either before (eight dogs) or 100 min after (eight dogs) oleic acid injection. In the control group (eight dogs) not treated with perindopril diacid, 150 min after oleic acid injection, PaO2 changed from 193 +/- 7 (mean +/- SEM) to 55 +/- 4 torr, venous admixture from 3 +/- 1% to 52 +/- 5%, cardiac index from 4.1 +/- 0.3 to 3.1 +/- 0.3 L/min X m2, mean pulmonary artery pressure from 13 +/- 1 to 17 +/- 1 mm Hg, dynamic compliance from 90 +/- 8 to 46 +/- 7 ml/cm H2O, and EVLW from 165 +/- 25 to 750 +/- 92 ml/m2. Administration of perindopril diacid reduced systemic BP by 20% but did not affect other hemodynamic variables, blood gases, or dynamic compliance. Maximum increases in EVLW were from 169 +/- 16 to 615 +/- 54 ml/m2 in the pretreated group and from 188 +/- 23 to 675 +/- 56 ml/m2 in the treated group (no significant difference from the control group). However, pretreatment with perindopril diacid significantly (p less than .05) slowed the rise in EVLW, which was lower 60 and 90 min after oleic acid injection compared to untreated dogs. Plasma renin activity and angiotensin I concentration increased after oleic acid injection.(ABSTRACT TRUNCATED AT 250 WORDS)
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001784:Blood Gas Analysis; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008176:Lung Volume Measurements; D019301:Oleic Acid; D009829:Oleic Acids / Q000009:adverse effects; D020913:Perindopril; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D009829:Oleic Acids; D019301:Oleic Acid; D012083:Renin; D020913:Perindopril