YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Cardiovascular Effects of Novel Potassium Channel Opener SKP-450 and SKP-818 in Isolated Rat Heart and Aorta

신규 합성 $K_{ATP}$ 통로 개방제인 SKP-450과 대사체 SKP-818의 흰쥐 적출 심장 및 대동맥에 대한 작용

  • Jung, Yi-Sook (School of Medicine, Ajou University) ;
  • Moon, Chang-Hyun (School of Medicine, Ajou University) ;
  • Yoo, Sung-Eun (Pharmacologic Screening Center, Korea, Research Institute of Chemical Technology) ;
  • Shin, Hwa-Sup (Pharmacologic Screening Center, Korea, Research Institute of Chemical Technology)
  • 정이숙 (아주대학교 의과대학 생리학교실) ;
  • 문창현 (아주대학교 의과대학 생리학교실) ;
  • 유성은 (한국화학연구소 의약활성실) ;
  • 신화섭 (한국화학연구소 의약활성실)
  • Published : 1997.04.01
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Abstract

The effect of potassium channel openers, SKP-450, SKP-818 and lemakalim have been compared in rat heart and aorta. In rat isolated heart, SKP-450 had a greater negative inotrop ic effect than lemakalim and KR-30818 against left ventricular developed pressure (LVDP) and double product of heart rate and LVDP (DP). In addition, SKP-450 had a greater effect than lemakalim and KR-30818 in increasing coronary flow, indicating a more potent vasodilating effect in coronary artery. Negative inotropic effect and coronary vasodilating effect of SKP-450 and SEP-818 were significantly reduced by 10 min-perfusion with $10^{-6}M$ glyburide, a selective blocker of ATP-sensitive potassium channel. In rat aorta, SKP-30450 and SKP-30818 as well as lemakalim induced powerful concentration-dependent relaxations against norepinephrinc-induced tone ($EC_{50},\;{\mu}M$ : SKP-30450, $0.107{\pm}0.009$; SKP-30818, $0.476{\pm}0.022$ ; lemakalim, $0.565{\pm}0.039$ ). These relaxant effects were significantly reduced by pretreatment with glyburide. In sununary, SKP-30450 and SKP-30818 showed greater negative inotropic and vasorelaxant effect than lemakalim in rat aorta with order of potency of SKP-30450 > SKP-30818 > lemakalim. These actions are suggested to be mediated at least in part by a mechanism which involves the opening of ATP-sensitive potassium channel.

Keywords

References

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