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KMID : 0648320100160020019
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Journal of The Korean Society of Hypertension
2010 Volume.16 No. 2 p.19 ~ p.27
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Effects of Losartan Administration on Uric acid Transporters in Rat Kidney
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Kim Su-A
Lee Chang-Hwa
Kang Chong-Myung
Kim Gheun-Ho
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Abstract
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Background : Losartan, an angiotensin II receptor blockade, has been reported to decrease the serum uric acid level through its uricosuric action. However, the mechanism by which losartan affects renal handling of uric acid in proximal tubule is not clear.
Methods : Male Sprague-Dawley rats were fed regular rat chow containing 1% oxonic acid in Experiment I, 5% uric acid in Experiment II and 2% oxonic acid plus 5% uric acid in Experiment III, respectively. Losartan was orally given (3mg/180g BW/d) in Experiment I and Experiment II and subcutaneously infused (10μg/kg/min) via osmotic minipumps in Experiment III for 7 days. From the harvested kidneys, semiquantitative immunoblotting and immunohistochemistry were carried out using antibodies to URAT1, OAT1, MRP4, and Na+/K+-ATPase α1 subunit.
Results : Semiquantitative immunoblotting revealed that the abundance of URAT1 protein in renal cortex was not significantly affected by losartan treatment. However, the OAT1 protein abundance in renal cortex was significantly increased by losartan treatment in Experiment I (100 ± 8% vs. 179 ± 25%, P < 0.01), Experiment II (100 ± 9% vs. 183 ± 12%, P < 0.01) and Experiment III (100 ± 13% vs. 177 ± 26%, P < 0.05). Consistent with these results, OAT1 immunohistochemistry showed a remarkable increase in immunoreactivity in the basolateral membrane of proximal tubules with losartan treatment.
Conclusion : The abundance of URAT1 protein may not be affected by losartan treatment in rat kidney. Instead, upregulation of OAT1 protein induced by losartan treatment may act to enhance urinary excretion of uric acid.
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KEYWORD
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uric acid, losartan, urate transporter, organic anion transport protein 1
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