Kidney Week

Abstract: TH-PO971

Renal NMDA Receptor Mediates the Amino Acid Induced Vasodilation Through Connecting Tubule-Glomerular Feedback (CTGF)

Session Information

• Pathology and Lab Medicine: Basic
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1501 Pathology and Lab Medicine: Basic

Authors

• Romero, Cesar A., Henry Ford Hospital, Detroit, Michigan, United States

Cesar A. Romero,

• Wang, Hong, Henry Ford Hospital, Detroit, Michigan, United States

Hong Wang,

• Ren, Yilin, Henry Ford Hospital, Detroit, Michigan, United States

Yilin Ren,

• Carretero, Oscar A., Henry Ford Hospital, Detroit, Michigan, United States

Oscar A. Carretero,

Background

The intravenous infusion of amino acids increase the renal blood flow and glomerular filtration rate, and it used to quantify the renal functional reserve. Similarly, high protein diet promotes the progression of chronic kidney diseases in part due to an increase in the renal blood flow, and glomerular pressure. Those glomerular effects are thought to be related to a vasodilation mediated by the amino acids that are released from the diet. However the vasodilator mechanism related to the amino acids in kidney is unknown. Kidney expresses the amino acid receptor N-methyl-D-aspartate (NMDA) that is activated by glutamate and glycine. Our lab described an intrinsic kidney feedback mechanism called CTGF that by sensing sodium in the connecting tubule (CNT) induces the dilation of the afferent arteriole (Af-Art). We hypothesize that in the kidney through the NMDA receptors the amino acids induce Af-Art dilation by activating CTGF.

Methods

By using double-perfusion of Af-Art and CNT technique in vitro (rabbit) and Stop-Flow Pressure (SFP) technique in vivo (Sprague Dawley Rat), we test the Af-Art dilation induced by CTGF when the CNT perfuse with glycine plus glutamate 10^-3M with or without the NMDA blocker MK-801.

Results

In vitro, in pre-constricted Af-Arts, addition of glycine plus glutamine to the CNT increases the Af-Art dilation (EC₅₀ 10.7) vs. control (EC₅₀ 24.5; p<0.001), and that dilation is blocked by CTGF blocker benzamil, suggesting that glycine plus glutamine enhanced CTGF. When we add the NMDA receptor blocker MK-801 to the CNT, the increased CTGF response is blunted. In vivo, the intratubular infusion of the amino acid induces vasodilation (SFP mmHg 37.9±2.6 vs. 28.6±1.9 control; P<0.01) and that vasodilation is blocked by benzamil.

Conclusion

Renal vasodilation induced by amino acid is mediated by the CTGF through the NMDA receptor in the connecting tubule. The activation of the CTGF by amino acids explain the basis of the renal functional reserve test and provide potential mechanism to prevent the renal damage associated with high protein diet.

Funding

• Other NIH Support