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Am J Physiol Regul Integr Comp Physiol (July 8, 2004). doi:10.1152/ajpregu.00169.2003
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Submitted on April 3, 2003
Accepted on June 28, 2004

Protein intake regulates the vasodilatory function of the kidney and the NMDA receptor expression

Larry A Slomowitz1, Francis B Gabbai1, Ser Khang1, Joseph Satriano1, Sonia Thareau1, Aihua Deng1, Scott C Thomson1, Roland C Blantz1, and Karen A Munger1*

1 Nephrology and Hypertension, University of California, San Diego and VA San Diego Healthcare System, San Diego, CA, USA

* To whom correspondence should be addressed. E-mail: kmunger{at}vapop.ucsd.edu.

Background: Glycine infusion in normal rats causes an increase in renal plasma flow and glomerular filtration rate. Although the renal response to glycine infusion is well characterized, the mechanism initiating this vasodilation is unknown. We have recently observed functionally active NMDA receptors in the kidney, located primarily in tubular structures. The mechanisms regulating activity of the NMDA receptor within the kidney are also unknown, as is its normal day-to-day functional role. Therefore, we hypothesize that dietary protein may impact the functional response to glycine infusion in both untreated rats and rats pretreated with angiotensin converting enzyme inhibitor (ACE) and furthermore, that renal NMDA receptors may be involved in the glycine response. Results: Surprisingly, 2 weeks of low protein diet (8% protein vs. 21% protein in Control diet) totally inhibited the glycine-induced vasodilation and GFR response. Associated with the absence of renal vasodilation, a significant reduction in proximal tubular reabsorption was observed during glycine infusion in low protein diet rats. In contrast to the disease models previously studied in our laboratory, administration of ACE inhibitors did not restore the glycine response in rats treated with low protein diet. Western blots of normal and low protein diet kidneys demonstrate that the newly described renal NMDA receptor is downregulated in rats fed low protein diet. Conclusions: Low protein feeding results in loss of glycine-induced vasodilation and GFR responses associated with decreased renal NMDA receptor expression. Kidney NMDA receptor expression is conditioned by protein intake, and this receptor may play an important role in the kidney vasodilatory response to glycine infusion and protein feeding in rats.




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