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
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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
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↵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.
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↵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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