title: Does inducible NOS have a protective role against hypoxia/reoxygenation injury in rat heart?
abstract: OBJECTIVE
  The present study analyzes the role of the nitric oxide (NO) derived from inducible NO synthase (iNOS) under cardiac hypoxia/reoxygenation situations.
  
  
  METHODS
  For this, we have designed a follow-up study of different parameters of cell and tissue damage in the heart of Wistar rats submitted for 30 min to acute hypobaric hypoxia, with or without prior treatment with the selective iNOS inhibitor N-(3-(aminomethyl)benzyl) acetamidine or 1400W (10 mg/kg). The rats were studied at 0 h, 12 h, and 5 days of reoxygenation, analyzing NO production (NOx), lipid peroxidation, apoptosis, and protein nitration expression and location. This is the first time-course study which analyzes the effects of the iNOS inhibition by 1400W during hypoxia/reoxygenation in the adult rat heart.
  
  
  RESULTS
  The results show that when 1400W was administered before the hypoxic episode, NOx levels fell, while both the lipid peroxidation level and the percentage of apoptotic cells rose throughout the reoxygenation period. Levels of nitrated proteins expression fell only at 12 h post-hypoxia.
  
  
  CONCLUSIONS
  The inhibition of iNOS raises the peroxidative and apoptotic level in the hypoxic heart indicating that this isoform may have a protective effect on this organ against hypoxia/reoxygenation injuries, and challenging the conventional wisdom that iNOS is deleterious under these conditions. These findings could help in the design of new treatments based on NO pharmacology against hypoxia/reoxygenation dysfunctions.
authors.affiliation: Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071, Jaén, Spain.
authors.forename: Alma
authors.initials: A
authors.lastname: Rus
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: del Moral
authors.forename: Francisco
authors.initials: F
authors.lastname: Molina
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Peinado
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat