Renal NMDA receptors independently stimulate proximal reabsorption and glomerular filtration

Department of Medicine, University of California School of Medicine and Veterans Affairs San Diego Healthcare System, San Diego, California Submitted 26 June 2008 ; accepted in final form 6 March 2009 N -methyl- D -aspartate receptors (NMDA) are expressed in the kidney, where little is known of their functional role. Several series of micropuncture experiments were performed in hydropenic rats using the NMDA channel blocker, MK801, and the NMDA coagonist, L -glycine, to probe NMDA for effects on single-nephron glomerular filtration rate (SNGFR) and proximal reabsorption ( J prox ). During intravenous infusion of MK801 or L -glycine, Henle's loop was perfused to manipulate SNGFR via tubuloglomerular feedback (TGF), thereby facilitating analysis of glomerulotubular balance. To confirm local actions on the kidney, MK801 was delivered to the glomerulus by microperfusion past the macula densa and to the proximal tubule by microperfusion into the early S1 segment. By all measures, MK801 acted on the glomerulus to reduce SNGFR, and acted on the proximal tubule to suppress J prox , while having no effect on the responsiveness of TGF. L -Glycine raised SNGFR, dampened the TGF response, and could not be proved to independently stimulate proximal reabsorption. NMDA exerts a tonic vasodilatory influence on the glomerulus and a proreabsorptive effect on the proximal tubule. These combined effects allow NMDA to modulate SNGFR with minimal impact on late proximal flow. The full effects of L -glycine infusion on proximal tubule and TGF response do not extrapolate from the response to NMDA blockade. N -methyl- D -aspartate receptors; L -glycine; tubuloglomerular feedback; glomerulotubular balance; micropuncture Address for reprint requests and other correspondence: S. C. Thomson, Univ. of California and VASDHS 9151, 3350 La Jolla Village Drive, San Diego, CA 92161 (e-mail: sthomson{at}ucsd.edu )