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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/F1433    most recent 00481.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, C.-C. Articles by Chen, C.-F. Search for Related Content PubMed PubMed Citation Articles by Yang, C.-C. Articles by Chen, C.-F.

NMDA receptor blocker ameliorates ischemia-reperfusion-induced renal dysfunction in rat kidneys

¹Department of Physiology, College of Medicine of National Taiwan University; ²School of Medicine, National Yang-Ming University; ³Taipei City Hospital-Heping Branch; Departments of ⁴Medical Research and ⁵Internal Medicine, National Taiwan University Hospital and College of Medicine of National Taiwan University; and ⁶School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan

Submitted 12 October 2007 ; accepted in final form 29 January 2008

N-methyl-D-aspartate (NMDA) receptor activated by glutamate/glycine is located in the kidneys. The NMDA receptor subunit NR1 is increased in damaged renal tissue. This study explored the role of NMDA receptors in ischemia-reperfusion-induced renal dysfunction in rats. With Western blot analysis and renal functional assay, NMDA receptor expression was evaluated, as well as its functional role in female Wistar rat kidneys after 45 min of unilateral ischemia followed by 24 h of reperfusion. The effects of intrarenal NMDA receptor agonist and antagonist on renal blood flow (RBF), glomerular filtration rate (GFR), urine volume (UV), sodium (U_NaV), and potassium (U_KV) excretion were determined. NMDA NR1 was present in the glomeruli, brush-border membrane, and outer medulla but not in the cortex and inner medulla. Homogenous distribution of non-NMDA GluR2/3, sparse kainate KA1, and undetectable group I of metabotropic glutamate receptor were noted in the control kidneys. Ischemia-reperfusion kidneys showed enhanced renal NR1, but not NR2C and GluR2/3 expression, and were associated with decreased GFR/RBF and natriuretic/diuretic responses. Intrarenal NMDA agonists significantly reduced GFR, UV, U_NaV, and U_KV but had no effect on blood pressure and RBF in sham control and ischemia-reperfusion kidneys. NMDA antagonist D-2-amino-5-phosphonopentanoic acid (D-AP-5) treatment completely abolished NMDA-induced renal dysfunction. D-AP-5 treatment significantly ameliorated ischemia-reperfusion-induced glomerular and tubular dysfunction by restoring decreased GFR, UV, and U_NaV levels. Ischemia-reperfusion upregulates renal NMDA NR1 receptor expression, leading to reduced glomerular and tubular function in the kidneys. The NMDA antagonist can ameliorate ischemia-reperfusion-induced renal dysfunction.

ischemia-reperfusion; kidney; glutamate; renal function

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				A. Deng and S. C. Thomson Renal NMDA receptors independently stimulate proximal reabsorption and glomerular filtration Am J Physiol Renal Physiol, May 1, 2009; 296(5): F976 - F982. [Abstract] [Full Text] [PDF]