Angiotensin-Converting Enzyme Inhibitor Captopril Prevents Oleic Acid-Induced Severe Acute Lung Injury in Rats

Abstract

Lack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress (ARDS). Recent evidence implies that angiotensin-converting enzyme (ACE) plays an important role in the pathogenesis of ALI. Pharmaceutical inhibitors of ACE have been used clinically for hypertension but not for ALI/ARDS yet. The objective was to study the effects of ACE inhibition with captopril on severe lung injury induced by oleic acid (OA) in rats. Oleic acid was intravenously injected into Sprague Dawley rats, followed by i.p. administration of captopril or saline control. Lung injury, endothelium damage and related molecules, and disturbance of coagulation were examined in comparison between the treated and the nontreated groups. An OA-induced ALI was featured with thickening of the alveolar septa, alveolar hemorrhage, and infiltration of inflammatory cells. Comparing with the nontreated OA group, the administration of captopril prevented the rats from OA-induced severe lungs injury, with a significantly lower lung injury score, less albumin content and infiltrated cells in the alveoli, decreased wet/dry weight ratio of the lung tissues, and improved lung function (PaO 2 per fraction of inspired oxygen). Captopril also dramatically reduced the expression of intercellular adhesion molecule<1 in the lung tissue and in the circulating endothelial cells in the blood, indicating a protective effect on endothelial cells activation/damage. Moreover, captopril treatment led to a blockage of nuclear factor .B activation in lung tissues and to the recovery of the fibrinolytic disturbance. Thus, our data suggest that the inhibition of ACE with its clinically used inhibitor offers protective effects on ALI/ARDS, implying the potential for therapeutic option.

Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study

“…54,55 In one study, it was shown that captopril application inhibited the NF-kb signal pathway and decreased the TNF-a and iNOS. 56,57 Therefore, ACE inhibitors and AT-2 antagonist inhibition can be used in preventing chronic complications induced by disease. 58,59 The increase in free oxygen radicals also leads to NF-kb activation at an early phase, and increases the release of proinflammatory cytokines.…”

Angiotensin-converting enzyme inhibitor use and protection against pneumonia in patients with diabetes

“…For example, ACE inhibitors have been linked to lower tumour necrosis factor-a and interleukin-6 levels in humans and reduced lipopolysaccharide-induced pulmonary neutrophil influx [11]. Furthermore, angiotensin II is believed to play an important role in tissue repair and remodelling [24] and inhibition of ACE has revealed an important role in acute lung injury-related endothelial cell damage and acute respiratory distress syndrome [10]. One possible mechanism behind this is the prevention of angiotensin II-induced transcription of the proinflammatory nuclear factor-kB [25].…”

“…To date, these studies were all conducted in patients with a history of stroke because induction of the cough reflex and prevention of aspiration was noted as the mechanism behind this protective effect [7,8]. Currently, there is accumulating evidence that ACE inhibitors also have different antiinflammatory and immunomodulatory effects [9][10][11], providing an additional explanation for a protective effect, which could also be present in patients without a history of stroke. Therefore, we assessed the effects of ACE inhibitor use on the risk of acquiring pneumonia in an unselected high-risk population of diabetic patients.…”

Angiotensin-converting enzyme I/D polymorphism and acute respiratory distress syndrome

“…24 ACE levels were elevated in BAL and administration of ACEI protected the rats from severe lungs injury. 6,7 Thus, ACE I/D polymorphism might be associated with increased ARDS risk.…”

“…6 Recently, a study indicated that the administration of captopril prevented rats from OA-induced severe lungs injury, with a significantly lower lung injury score, less albumin content and infiltrated cells in the alveoli, decreased wet/dry weight ratio of the lung tissues and improved lung function (PaO2 per fraction of inspired oxygen). 7 The ACE gene is located on chromosome 17q35 and consists of 26 exons spread over approximately 24 kb. The intron 16 of the ACE gene contains a restriction fragment length polymorphism consisting of the presence (insertion, I) or absence (deletion, D) of a 287-bp alu repeat sequence.…”