MISC

2002年

Inhibitors of pentose phosphate pathway cause vasodilation: Involvement of voltage-gated potassium channels

Journal of Pharmacology and Experimental Therapeutics
  • Sachin A. Gupte
  • ,
  • Kai-Xun Li
  • ,
  • Takao Okada
  • ,
  • Koichi Sato
  • ,
  • Masahiko Oka

301
1
開始ページ
299
終了ページ
305
記述言語
英語
掲載種別
DOI
10.1124/jpet.301.1.299

Cytosolic reducing cofactors, such as NADPH and NADH, are thought to regulate vascular smooth muscle ion channel activity and vascular tone. In this study, the effects of pentose phosphate pathway (PPP) inhibitors, 6-aminonicotinamide (6-AN), epiandrosterone (EPI), and dehydroepiandrosterone (DHEA), on vascular tone were studied in isolated perfused lungs and pulmonary artery (PA) and aortic rings from rats. In addition, effects of 6-AN on voltage-gated K+ (Kv) current in PA smooth muscle cells (SMCs) were also examined. Pretreatment of lungs with 6-AN and EPI reduced the pressor response to acute hypoxia and decreased tissue NADPH levels. 6-AN, EPI, and DHEA relaxed isolated PA and aortic rings precontracted with 30 mM KCl in a dose-dependent manner. The PPP inhibitor-induced PA relaxations were reduced in PA rings precontracted with 80 mM KCI but not by pretreatment with nitro-L-arginine or endothelial removal. Pretreatment of PA rings with tetraethyl-ammonium chloride or 4-aminopyridine caused rightward shifts of concentration-relaxation curves for 6-AN, EPI, and DHEA. In contrast, glybenclamide, charybdotoxin, or apamin did not inhibit the relaxant effects of 6-AN, EPI, and DHEA. 6-AN caused an increase in Kv current in PASMC. These results indicate that reduction of NADPH by the PPP inhibitors causes vasodilation at least partly through opening of Kv channels.

リンク情報
DOI
https://doi.org/10.1124/jpet.301.1.299
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/11907187
ID情報
  • DOI : 10.1124/jpet.301.1.299
  • ISSN : 0022-3565
  • PubMed ID : 11907187
  • SCOPUS ID : 0036196176

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