Toshihiro Yorozuya⁽¹⁾, Naoto Adachi⁽²⁾, Masao Soutani⁽³⁾, Kazuo Nakanishi⁽⁴⁾, Kentaro Dote⁽⁵⁾, Shigeo Kimura⁽⁶⁾, Takumi Nagaro⁽⁷⁾, Tatsuru Arai^{(8)
(1)(2)(3)(7)(8)}Ehime-university School of Medicine - Japan
^(4)(5)(6)Ehime university School of Medicine - Japan

Contact address:

Toshihiro Yorozuya Ehime-university School of Medicine Shitsukawa, Shigenobu-cho Onsen-gun Ehime pref. 791-0295 Japan yoro@hypnos.m.ehime-u.ac.jp

	[Pharmacology]	[Cardiolovascular Diseases]

ABSTRACT

There are many studies that glucocorticoids improve ischemia-induced myocardial injury. However, the mechanism underlying the improvement has been unclear. Since adenosine 5´-triphosphate (ATP) provides energy for contraction and maintains membrane functional integrity, we investigated the effect of dexamethasone, a pure glucocorticoid, on the hypoxic reduction of ATP in the mouse heart. Male ddY mice were assigned to saline and dexamethasone (5 mg/kg, ip) groups. Three hours after administration, mice were decapitated, and the heart was immediately removed and incubated in a glucose-free hypoxic phosphate buffer equilibrated with nitrogen (pH 7.4, 37 degrees C). Then, the heart was frozen in liquid nitrogen after 0, 5, 10, or 20 minutes of incubation. The ATP content of the heart was determined by a high-performance liquid chromatography coupled with UV detection system. The ATP concentration did not differ between the saline and dexamethasone groups when the hearts were frozen immediately after removal. The values were 1568 +/- 470 and 1727 +/- 259 nmol/g (mean +/- SD), respectively. Hypoxia for 5 minutes decreased ATP contentto 330 +/- 130 nmol/g in the saline group. ATP decrease as a result of hypoxia was markedly suppressed by dexamethasone treatment. The ATP level after 5 minutes of hypoxia was 1085 +/- 296 nmol/g. Although the long duration of hypoxia further lowered the ATP content in each groups, no difference was found between the two groups after 10 or 20 minutes of hypoxia. Dexamethasone-induced reduction of ATP consumption during hypoxia may be a mechanism responsible for the improvement of ischemic myocardial damage.

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Keywords: hypoxia - myocardium - adenosine 5´-triphosphate - dexamethasone - mice -

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[ABSTRACT] [INTRODUCTION] [MATERIAL & METHODS] [RESULTS] [FIGURES] [DISCUSSION] [CONCLUSIONS] [BIBLIOGRAPHY] [Discussion Board]

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	[Pharmacology]	[Cardiolovascular Diseases]

Toshihiro Yorozuya, Naoto Adachi, Masao Soutani, Kazuo Nakanishi, Kentaro Dote, Shigeo Kimura, Takumi Nagaro, Tatsuru Arai
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Last update: 14/01/00