title: Protein intake regulates the vasodilatory function of the kidney and NMDA receptor expression.
abstract: Glycine infusion in normal rats causes an increase in renal plasma flow and glomerular filtration rate (GFR). Although the renal response to glycine infusion is well characterized, the mechanism initiating this vasodilation is unknown. We recently observed functionally active N-methyl-d-aspartate (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 (ACE) inhibitor and, furthermore, that renal NMDA receptors may be involved in the glycine response. Surprisingly, 2 wk 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 a low-protein diet. 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.
authors.affiliation: Department of Medicine, University of California San Diego, Veterans Administration San Diego Healthcare System, 92161, USA
authors.forename: Larry A
authors.initials: LA
authors.lastname: Slomowitz
authors.forename: Francis B
authors.initials: FB
authors.lastname: Gabbai
authors.forename: Ser J
authors.initials: SJ
authors.lastname: Khang
authors.forename: Joseph
authors.initials: J
authors.lastname: Satriano
authors.forename: Sonia
authors.initials: S
authors.lastname: Thareau
authors.forename: Aihua
authors.initials: A
authors.lastname: Deng
authors.forename: Scott C
authors.initials: SC
authors.lastname: Thomson
authors.forename: Roland C
authors.initials: RC
authors.lastname: Blantz
authors.forename: Karen A
authors.initials: KA
authors.lastname: Munger
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology; D006874:Hydrostatic Pressure; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D008297:Male; D011502:Protein-Energy Malnutrition / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004044:Dietary Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D002216:Captopril; D005998:Glycine