Abstract P212: NMDA Receptor Glutn2c Deficient Mouse Associates With Hypertension

Abstract

Introduction: N-methyl-D-Aspartate (NMDA) receptors are glutamate receptors located in the CNS and peripheral tissues. We previously showed that kidney NMDA receptors in the connecting/collecting ducts (CNT/CCD) participate in renal autoregulation and kidney vasodilation. We also showed that the use of non-specific NMDA inhibitors increases blood pressure. This work aims to identify which NMDA receptor subtypes are associated with hypertension. Methods: We simultaneously evaluated the expression of GluN2C and 2D in the CNT/CCD by using in-situ hybridization (RNA scope) with the presence of CNT/CCD marker AQP-2 using immunofluorescence. Blood pressure was evaluated in C57B mice and global genetic ablated mice on C57B background: GluN2C-KO or GluN2D-KO. Blood pressure was measured using the tail-cuff method three times a week for two weeks after three sesión training. We used both male and female mice. Animals were fed on regular and high salt diets (4%). Results: RNA expression of NMDA subunits 2C and 2D were found to be present in AQP2-positive regions from mouse kidneys, compatible with CNT/CCD regions. The average systolic blood pressure (SBP) for C57B control mice was 105.6±10.5 mmHg; on GluN2C-KO mice, SBP was 114.6±7.3 mmHg, significantly elevated compared to the matched C57B control mice (p<0.01), and GluN2D mice’s SBP was 111.6±10.4 mmHg with no significant differences from the matched control (111.1±4.6 mmHg; p=0.93). No difference was observed between male and female mice in both genetically ablated mice. After a challenge with a high salt diet, blood pressure did not change in all three groups. Conclusion: NMDA receptors subunits GluN2C and GluN2D are expressed in the CNT/CCD region. The genetic absence of GlutN2C is associated with high blood pressure; however, the lack of GLUN2D did not change SBP. No salt sensitivity was observed in any of the genetically ablated mice. Future work will explore the role of renal hemodynamics in these blood pressure phenotypes.