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Soluble Guanylate Cyclase Redox State Under Hypoxia or Hypoxia/Reoxygenation in Isolated Monkey Coronary Arteries.
MedLine Citation:
PMID:  24859780     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hypoxia or hypoxia/reoxygenation impairs nitric oxide (NO)-mediated relaxation through the increase in superoxide generation in monkey coronary arteries. Soluble guanylate cyclase (sGC), the target enzyme of NO, has been shown to change from the NO-sensitive reduced form to the NO-insensitive oxidized/heme-free form under substantial oxidative stress, so the present study investigated whether hypoxia or hypoxia/reoxygenation influences sGC redox equilibrium. In isolated monkey coronary arteries without endothelium, the relaxation caused by the sGC stimulator BAY 41-2272 (Emax: 93.3% ± 2.2%) was somewhat impaired under hypoxia (Emax: 86.3% ± 2.6%) or hypoxia/reoxygenation (Emax: 86.1% ± 3.2%), whereas that by the sGC activator BAY 60-2770 (Emax: 86.0% ± 3.2%) was significantly augmented under hypoxia (Emax: 94.4% ± 1.3%) or hypoxia/reoxygenation (Emax: 95.5% ± 1.1%). In addition, cGMP formation in response to BAY 41-2272 and BAY 60-2770 was inhibited and stimulated, respectively, under hypoxia or hypoxia/reoxygenation. The effects of hypoxia or hypoxia/reoxygenation on BAY 41-2272- and BAY 60-2770-induced vasorelaxation were completely canceled by the treatment with the superoxide dismutase mimetic tempol. These findings suggest that sGC redox equilibrium in the coronary artery is shifted towards the NO-insensitive form under hypoxia or hypoxia/reoxygenation and that superoxide seems to play an important role in this shift.
Authors:
Masashi Tawa; Ayman Geddawy; Takashi Shimosato; Hirotaka Iwasaki; Takeshi Imamura; Tomio Okamura
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-23
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  -     ISSN:  1347-8648     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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