Vasodilatory N-methyl-D-aspartate receptors are constitutively expressed in rat kidney.
N-methyl-D-aspartate receptor (NMDA-R) is an amino acid receptor and membrane calcium channel. NMDA-R is activated by binding of coagonists, L-glutamine and L-glycine. In the brain, calcium entry via NMDA-R activates type I nitric oxide synthase (NOS I). The kidney also contains NOS I and vasodilates in response to L-glycine. In this study, NMDA-R mRNA was demonstrated in rat kidney cortex by reverse transcriptase-PCR and cDNA sequencing. NMDA-R protein was demonstrated in kidney cortex by immunoblotting. To study the functional role of renal NMDA-R, renal hemodynamic effects of NMDA-R inhibition were assessed in rats using a blocker of the NMDA calcium channel (75 mg/kg MK-801 intraperitoneally) or an inhibitor of glycine binding to NMDA-R (30 mg/kg 5,7-dichlorokynurenic acid intraperitoneally). Renal blood flow was measured by perivascular pulse Doppler. GFR was measured by 3H-inulin clearance. Measurements were made before and during glycine infusion. Both NMDA-R antagonists caused renal vasoconstriction and attenuated the renal vasodilatory response to glycine infusion. These effects were not mediated by the renal nerves. The glycine response was not inhibited by aortic snare used to mimic the effects of NMDA-R inhibitors on basal renal blood flow. NMDA-R are expressed in kidney cortex, where they exert a tonic vasodilatory influence and may account for the vasodilatory response to glycine infusion.
Deng
Aihua
A
Department of Medicine, University of California and Veterans Affairs Medical Center, San Diego, California.
Valdivielso
Jose M
JM
Munger
Karen A
KA
Blantz
Roland C
RC
Thomson
Scott C
SC
D000704:Analysis of Variance; D000818:Animals; D018076:DNA, Complementary / Q000032:analysis; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D005998:Glycine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine