title: Hydrogen peroxide enhances vasodilatation by increasing dimerization of cGMP-dependent protein kinase type Iα.
abstract: BACKGROUND
  cGMP-dependent protein kinase type I (PKG I) plays a key role in vasodilatation caused by cGMP-elevating agents. It is a homodimer in mammalian cells, existing as 2 isoforms, Iα and Iβ. The aim of the present study was both to determine whether PKG I dimerization and activity are modulated by hydrogen peroxide (H(2)O(2)) and its influence on vasodilatation.
  
  
  RESULTS
  The dimers and monomers of total PKG I and PKG Iβ were analyzed by Western blotting. PKG I activity was assayed by measuring the incorporation of (32)P into BPDEtide. Changes in vessels tension were determined by organ chamber technique. In isolated porcine coronary arteries, H(2)O(2) increased the dimers of total PKG I in a concentration-dependent manner, but had no effect on dimerization of PKG Iβ. The dimerization of PKG I caused by H(2)O(2) was prevented by catalase but not by deferoxamine and tiron. H(2)O(2) promoted the translocation of PKG I from cytoplasm to membrane. H(2)O(2) enhanced the activity of PKG I and relaxations of porcine coronary arteries to the nitric oxide donor and 8-Br-cGMP. Inhibition of catalase under in vivo conditions significantly decreased rat mean arterial pressure, which was associated with increased dimerization of PKG I.
  
  
  CONCLUSIONS
  The present study suggests that H(2)O(2) may enhance the activity of PKG Iα-and PKG I-dependent vasodilatation via increased dimerization of the enzyme.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Dou
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zheng
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Xu
authors.forename: Liping
authors.initials: L
authors.lastname: Ye
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002374:Catalase / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; C016276:8-bromocyclic GMP; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D006861:Hydrogen Peroxide; D002374:Catalase; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D003676:Deferoxamine; D000640:Amitrole