Submitted on June 26, 2008
Revised on March 6, 2009
Accepted on March 6, 2009
RENAL NMDA RECEPTORS INDEPENDENTLY STIMULATE PROXIMAL REABSORPTION AND GLOMERULAR FILTRATION
Aihua Deng1 and Scott C. Thomson2*
1 University of California
2 University of California and VA Medical Center
* To whom correspondence should be addressed. E-mail: sthomson{at}ucsd.edu.
Background: N-methyl-D-aspartate receptors (NMDA) are expressed in the kidney, where little is known of their functional role. Methods: Several series of micropuncture experiments were performed in hydropenic rats using the NMDA channel blocker, MK801, and the NMDA co-agonist, L-glycine, to probe NMDA for effects on single nephron GFR (SNGFR) and proximal reabsorption (Jprox). 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. Results: By all measures, MK801 acted on the glomerulus to reduce SNGFR, and acted on the proximal tubule to suppress Jprox, 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. Conclusion: NMDA exerts a tonic vasodilatory influence on the glomerulus and a pro-reabsorptive 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.
