Effect of an ATP sensitive potassium channel opener, levcromakalim, on coronary arterial microvessels in the beating canine heart

Kouichi Sato, Hiroshi Kanatsuka, Nobuyo Sekiguchi, Kenjiro Akai, Yan Wang, Akihiko Sugimura, Toshinobu Kumagai, Tatsuya Komaru, Kunio Shirato

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30 Citations (Scopus)

Abstract

Objective: The aim was to clarify the site in the coronary microcirculation that is dilated by an ATP sensitive potassium channel opener, levcromakalim, and to examine whether the magnitude of dilatation is size dependent. Methods: Coronary arterial microvessels were observed through an intravital microscope equipped with a floating objective in beating canine left ventricles in situ. Flow velocity of the left anterior descending coronary artery was measured with a suction-type Doppler probe. Heart rate and aortic pressure were maintained at control levels throughout the experiments. Three doses of levcromakalim (0.01-1.0 μg·kg-1·min-1) or a single dose (1.0 μg·kg-1 ·min-1) were infused into the coronary artery in groups, with or without intracoronary glibenclamide pretreatment (200 or 400 μg·kg-1). The effect of levcromakalim on different sized vessels was assessed by dividing them into three groups according to control diameter (small, internal diameter <100 μm; medium, {slanted equal to or greater-than} 100, <200 μm; large, {slanted equal to or greater-than}200 μm). Results: The lowest dose of levcromakalim dilated only the small vessels. The two higher doses dilated vessels of all sizes, but the magnitude of dilatation was greater in the small vessel group than in the other two groups. Coronary resistance significantly decreased dose dependently during the infusion of 0.1 and 1.0 μg·kgt-1·min-1 of levcromakalim. Pretreatment with glibenclamide markedly attenuated the levcromakalim induced dilatation of all vessel groups and the reduction in coronary vascular resistance. Conclusions: Levcromakalim heterogeneously dilates coronary arterial microvessels via the opening of ATP sensitive potassium channels, and small vessels are more sensitive to levcromakalim.

Original languageEnglish
Pages (from-to)1780-1786
Number of pages7
JournalCardiovascular Research
Volume28
Issue number12
Publication statusPublished - 1994 Dec 1

Keywords

  • ATP sensitive potassium channel
  • coronary microcirculation
  • cromakalim
  • glibenclamide
  • lemakalim

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Sato, K., Kanatsuka, H., Sekiguchi, N., Akai, K., Wang, Y., Sugimura, A., Kumagai, T., Komaru, T., & Shirato, K. (1994). Effect of an ATP sensitive potassium channel opener, levcromakalim, on coronary arterial microvessels in the beating canine heart. Cardiovascular Research, 28(12), 1780-1786.