Abstract:
OBJECTIVE:To study whether pretreatment of newborn lungs by captopril inhibits meconium-induced lung injury and inflammatory cytokine expression. DESIGN:Four groups of 2-week-old rabbit pups were used for the study: group 1, saline instilled rabbits; group 2, captopril-pretreated rabbits; group 3, meconium-instilled rabbits; and group 4, captopril-pretreated and then meconium-instilled rabbits. Each group was studied at different time points: 0, 2, 4, 8, and 24 hours after instillation of meconium. Experiments were done at the University of Illinois and Michael Reese Hospital at Chicago. After treatment and instillation of meconium, the right lung was fixed with formalin, and 2-mum slices were obtained for immunohistochemistry. The left lung was used for obtaining of lung lavage and measurement of total proteins (for enzyme-linked immunosorbent assay) and mRNA (for reverse transcription-polymerase chain reaction) purification. RESULTS:We found that meconium induces inflammatory cytokine expression and apoptotic lung cell death. In situ end labeling revealed a dramatic DNA fragmentation in the meconium group, which supports the presence of apoptosis. Using enzyme-linked immunosorbent assay, we demonstrated increase of interleukin 6 and interleukin 8 cytokines in meconium-instilled lungs, which were significantly decreased in captopril-pretreated lungs. Captopril pretreatment also decreased meconium-induced cell death and angiotensinogen expression. We believe this effect is explained by the ability of captopril to decrease processing of ANGEN to angiotensinogen (ANG) I and finally to ANG II. It suggests that captopril inhibits ANG II-induced lung cell apoptosis. CONCLUSION:Our results demonstrate that captopril pretreatment significantly inhibits meconium-induced lung cell death, cytokine, and ANGEN expression in newborn lungs.
journal_name
Pediatricsjournal_title
Pediatricsauthors
Zagariya A,Bhat R,Navale S,Chari G,Vidyasagar Ddoi
10.1542/peds.2005-0274subject
Has Abstractpub_date
2006-05-01 00:00:00pages
1722-7issue
5eissn
0031-4005issn
1098-4275pii
117/5/1722journal_volume
117pub_type
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