title: Chronic hypoxia increases peroxynitrite, MMP9 expression, and collagen accumulation in fetal guinea pig hearts.
abstract: BACKGROUND
  Chronic hypoxia increases the expression of inducible nitric oxide synthase (iNOS) mRNA and protein levels in fetal guinea pig heart ventricles. Excessive generation of nitric oxide (NO) can induce nitrosative stress leading to the formation of peroxynitrite, which can upregulate the expression of matrix metalloproteinases (MMPs). This study tested the hypothesis that maternal hypoxia increases fetal cardiac MMP9 and collagen through peroxynitrite generation in fetal hearts.
  
  
  RESULTS
  In heart ventricles, levels of malondialdehyde, 3-nitrotyrosine (3-NT), MMP9, and collagen were increased in hypoxic (HPX) vs. normoxic (NMX) fetal guinea pigs.
  
  
  CONCLUSIONS
  Thus, maternal hypoxia induces oxidative-nitrosative stress and alters protein expression of the extracellular matrix (ECM) through upregulation of the iNOS pathway in fetal heart ventricles. This identifies iNOS-derived NO as an important stimulus for initiating the adverse effects of peroxynitrite in HPX fetal hearts.
  
  
  METHODS
  Pregnant guinea pigs were exposed to normoxia (room air) or hypoxia (10.5% O(2), 14 d) before term (term ≈ 65 d) and administered water, L-N6-(1-iminoethyl)-lysine (LNIL), an iNOS inhibitor, or N-acetylcysteine (NAC), an antioxidant.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Lashauna C
authors.initials: LC
authors.lastname: Evans
authors.forename: Hongshan
authors.initials: H
authors.lastname: Liu
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Pinkas
authors.forename: Loren P
authors.initials: LP
authors.lastname: Thompson
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005318:Fetal Heart / Q000378:metabolism*; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism*; D015227:Lipid Peroxidation; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009929:Organ Size; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011247:Pregnancy; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9; D000111:Acetylcysteine