title: GATA-4 transcription factor regulates cardiac COX-2 expression induced by nicorandil in left ventricle of rats.
abstract: OBJECTIVE
  Cardioprotective effects induced by delayed ischemic preconditioning and by nicorandil are mediated via expression of cardioprotective factors such as COX-2. The present study was undertaken to evaluate whether nicorandil could induce COX-2 in rats and to elucidate its mode of induction pharmacologically.
  
  
  RESULTS
  Three hours after administration of nicorandil (10 mg/kg, p.o.), COX-2 mRNA and protein were significantly increased in the left ventricle, although other cardioprotective factors (Bcl-2, eNOS, hexokinase, HSP, and iNOS) were not increased. This COX-2 induction in the left ventricle was preceded by induction of GATA-4, which was significant from 1 h after administration. Ventricular levels of 6-keto-prostaglandin F1α were increased 6 h after administration. Although pinacidil or isosorbide dinitrate alone did not increase COX-2 mRNA, their combined application significantly increased COX-2 mRNA. Moreover, although glibenclamide or ODQ each partly inhibited the induction of COX-2 mRNA by nicorandil, their combined application significantly inhibited it. These results suggest that nicorandil induces COX-2 protein through both the activation of KATP channels and guanylate cyclase.
  
  
  CONCLUSIONS
  The present study demonstrated that nicorandil induces COX-2 via GATA-4 induction in the heart through both KATP channel activation and its nitrate-like properties.
authors.affiliation: Product Research Department, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Serizawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Yogo
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tashiro
authors.forename: Ken
authors.initials: K
authors.lastname: Aizawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ishizuka
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics*; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020108:Nicorandil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D050991:GATA4 Transcription Factor; D054086:KATP Channels; D012333:RNA, Messenger; D014665:Vasodilator Agents; D020108:Nicorandil; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2; D006162:Guanylate Cyclase; D005905:Glyburide