Rosiglitazone preserves pulmonary vascular function in lambs with increased pulmonary blood flow

Peter E. Oishi, Shruti Sharma, Sanjeev A. Datar, Sanjiv Kumar, Saurabh Aggarwal, Qing Lu, Gary W Raff, Anthony Azakie, Jong Hau Hsu, Eniko Sajti, Sohrab Fratz, Stephen M. Black, Jeffrey R. Fineman

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect.Methods:An aorta-to-pulmonary-artery shunt was placed in 11 fetal lambs. Lambs received the PPAR-γ agonist rosiglitazone (RG, 3 mg/kg/d, n = 6) or vehicle (n = 5) for 4 wk. Lung tissue from five normal 4-wk-old lambs was used for comparisons.Results:At 4 wk, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased with inhaled nitric oxide (NO) in RG-and vehicle-treated shunt lambs. PAP and PVR decreased with acetylcholine (Ach) in RG-treated, but not vehicle-treated, shunt lambs. In vehicle-treated shunt lambs, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT) levels were increased, and Ser1177 endothelial NO synthase (eNOS) protein was decreased as compared with normal lambs. In RG-treated shunt lambs, NOx, Ser1177 eNOS protein, and eNOS activity were increased, and NADPH activity, rac1, superoxide levels, and 3-NT levels were decreased, as compared with vehicle-treated shunt lambs. PPAR-γ protein expression was lower in vehicle-treated shunt lambs than in normal and RG-treated shunt lambs.Conclusion:The PPAR-γ agonist RG prevents the loss of agonist-induced endothelium-dependent pulmonary vascular relaxation in lambs with increased PBF, in part, due to decreased oxidative stress and/or increased NO production.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalPediatric Research
Volume73
Issue number1
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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