Activation of renal NMDA receptors with glutamate modulates oxygen consumption and hemodynamics

Abstract

We have previously reported functional NMDA receptors in rat kidney (J Am Soc Neph, 13:1381, 2002). NMDA is required for glycine-induced increases in GFR and renal plasma flow (RPF). Since NMDA receptors require both glycine and glutamate for activation, we compared the effects of both on GFR and RPF (ml/min), renal oxygen consumption (QO2, ml/min), sodium transport (TNa, mM/min), and QO2/TNa. Groups: 1) GLU (glutamate infusion, 1.3 M, 1.6 ml/hr, IV); 2) GLU+MK801 (NMDA antagonist; 0.5mg/kg, IV bolus); 3) GLY (glycine infusion, 2.6 M, 1.6 ml/hr, IV); 4) GLY+MK801. Experiments were conducted in anesthetized male Wistar rats (250–300 gms, n=6 each group). Mean±stdev, *p<0.05 paired T-test. This is the first report of infused glutamate on renal hemodynamics. Given the ample levels of endogenous glutamate in the kidney, exogenous infusion of glutamate resulted in surprisingly robust increases in GFR and RPF, similar to glycine infusion. Both agonists increased TNa, but only GLU increased QO2/TNa. MK801 prevented these changes. These studies reiterate the importance of the renal NMDA receptor in kidney function and also point to a role for exogenous and endogenous glutamate in regulating normal renal function. Funded by NIH NIDDK RO-1 DK 62831-2.