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Research ArticleArticle

Adenosine A1 Receptor Antagonist KW-3902 Prevents Hypoxia-Induced Renal Vasoconstriction

Akira Nishiyama, Akira Miyatake, Yasuharu Aki, Toshiki Fukui, Matlubur Rahman, Shoji Kimura and Youichi Abe
Journal of Pharmacology and Experimental Therapeutics December 1999, 291 (3) 988-993;
Akira Nishiyama
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Akira Miyatake
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Yasuharu Aki
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Toshiki Fukui
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Matlubur Rahman
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Shoji Kimura
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Youichi Abe
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Abstract

Studies were carried out to determine the intrarenal adenosine production during hypoxia, and the protective effects of a selective adenosine A1 receptor antagonist 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902) on hypoxia-induced renal hemodynamic changes. We used an in vivo microdialysis method and measured the renal interstitial concentration of adenosine in response to hypoxic exposure in anesthetized mechanically ventilated rabbits. Normocapnic systemic hypoxia (PaO2 = 32 ± 6 mm Hg) caused a significant decrease in renal blood flow and increase in renal vascular resistance, indicating a renal vasoconstriction. The basal interstitial concentration of adenosine in the cortex was 293 ± 70 nM, which was significantly higher than that in the medulla (170 ± 23 nM). Five minutes after beginning hypoxia, the renal interstitial concentration of adenosine approximately tripled in the cortex and doubled in the medulla. During treatment with KW-3902, hypoxemia caused a similar increase in the adenosine concentration compared with that in the absence of KW-3902. The administration of KW-3902, however, significantly attenuated hypoxia-induced reduction in renal blood flow. These results suggest that adenosine was involved in hypoxia-induced renal vasoconstriction via its effects on adenosine A1 receptors, and that KW-3902 had a partial protective effect against renal vasoconstriction during hypoxemia.

Footnotes

  • Send reprint requests to: Youichi Abe., M.D., Ph.D., Department of Pharmacology, Kagawa Medical University,1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail: yakuri{at}kms.ac.jp

  • ↵1 This work was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Science, and Culture of Japan. Part of this work was presented at the 31st Annual Meetings of the American Society of Nephrology, Philladelphia, PA, 1998.

  • ↵2 Department of Physiology, SL-39, Tulane University School of Medicine, 1430 Tulane Ave., New Orleans, LA 70112.

  • Abbreviations:
    RBF
    renal blood flow
    KW-3902
    8-(noradamantan-3-yl)-1,3-dipropylxanthine
    MAP
    mean arterial pressure
    EHNA
    erythro-9-(2-hydroxy-3-nonyl)adenine
    RVR
    renal vascular resistance
    ANG II
    angiotensin II
    NE
    norepinephrine
    • Received March 3, 1999.
    • Accepted August 6, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 3
1 Dec 1999
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Research ArticleArticle

Adenosine A1 Receptor Antagonist KW-3902 Prevents Hypoxia-Induced Renal Vasoconstriction

Akira Nishiyama, Akira Miyatake, Yasuharu Aki, Toshiki Fukui, Matlubur Rahman, Shoji Kimura and Youichi Abe
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 988-993;

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Research ArticleArticle

Adenosine A1 Receptor Antagonist KW-3902 Prevents Hypoxia-Induced Renal Vasoconstriction

Akira Nishiyama, Akira Miyatake, Yasuharu Aki, Toshiki Fukui, Matlubur Rahman, Shoji Kimura and Youichi Abe
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 988-993;
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