Mechanisms of hypoxic coronary vasodilatation in isolated perfused rat hearts

Isamu Kamekura, Kenji Okumura, Hideo Matsui, Kichiro Murase, Shinji Mokuno, Yukio Toki, Yoshihito Nakashima, Takayuki Ito

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16 Citations (Scopus)

Abstract

We pharmacologically investigated the potential involvement of nitric oxide (NO), prostacyclin, adenosine, adenosine triphosphate (ATP)-sensitive K (K(ATP)) channel opening and Ca2+-activated K (K(Ca)) channel opening in coronary vasodilatation during 15 min of hypoxia in isolated rat hearts perfused at a constant pressure of 70 mm Fig. The coronary flow suppressed by 10-4 M N(ω)-nitro-L-arginine methyl ester (L-NAME), which corresponds to the NO-dependent flow, decreased to almost zero during hypoxia. In contrast, the NO-dependent coronary flow amounted to ~40% of the total coronary flow during normoxia. The suppression of coronary flow by 10-5 M 8- phenyltheophylline (8-PT), which corresponds to the adenosine-dependent flow, was remarkable in the middle and the late phases of a 15-min hypoxia. The coronary flow suppressed by 2 x 10-6 M glibenclamide, which corresponds to the K(ATP) channel opening-dependent flow, depended on the agents added to the perfusate. However, there was a marked increase in coronary flow in the early phase of hypoxia in the heart perfused with the combination of 8-PT, 10-2 M tetraethylammonium (TEA) and L-NAME. During hypoxia, the coronary flow suppressed by TEA, which corresponds mainly to the K(Ca) channel opening-dependent flow, also depended on the agents added to the perfusate. However, during reoxygenation, there was a transient significant increase in any combination of the agents. Our study suggests that hypoxia almost completely inhibits NO production, and that K(ATP) channel opening immediately after hypoxia and subsequent enhanced adenosine production cause a marked hypoxic coronary vasodilatation. It also suggests that K(Ca) channel opening causes vasodilatation during reoxygenation.

Original languageEnglish
Pages (from-to)836-842
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume33
Issue number6
DOIs
Publication statusPublished - 06-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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