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(Na)V), and
potassium (U(K)V) 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(Na)V, and U(K)V 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(Na)V 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.