O37 LINK BETWEEN NMDA RECEPTOR GluN2C DEFICIENCY AND HYPERTENSION IN MICE

Abstract

N-methyl-D-aspartate (NMDA) receptors are glutamate receptors located in the CNS and peripheral tissues. We previously demonstrated that kidney NMDA receptors in the connecting/collecting ducts (CNT/CCD) participate in renal autoregulation and kidney vasodilation. Additionally, we found that the use of non-specific NMDA inhibitors increases blood pressure. This study aims to identify which NMDA receptor subtypes are associated with hypertension. We evaluated the RNA transcription of the Grin2C gene (GluN2C subunit) and the Grin2D gene (GluN2D subunit) in the CNT/CCD using in-situ hybridization RNA scope, along with the presence of the CNT/CCD marker AQP-2. Blood pressure was evaluated in C57B mice and global genetic ablated mice on a C57B background: GluN2C-KO and GluN2D-KO. Blood pressure was measured using the tail-cuff method three times a week for two weeks following a three-session training period. Both male and female mice were used. Animals were fed regular and high salt diets (4%). RNA expression of NMDA subunits 2C and 2D was found in AQP2-positive regions of mouse kidneys, consistent with CNT/CCD regions. Females had higher Grin2C transcription levels than males (p<0.01). The average systolic blood pressure (SBP) for C57B control mice was 105.6±10.5 mmHg. SBP in GluN2C-KO mice was 114.6±7.3 mmHg, significantly elevated compared to the matched C57B control mice (p<0.01). SBP in GluN2D-KO mice was 111.6±10.4 mmHg, with no significant differences from the matched control (111.1±4.6 mmHg; p=0.93). GluN2C-KO female tends to have higher SBP tan males, however the difference was not statistical significant. Following a high salt diet challenge, blood pressure did not change in any of the three groups. NMDA receptor subunits GluN2C and GluN2D are expressed in the CNT/CCD region. The genetic absence of GluN2C is associated with increased blood pressure, whereas the lack of GluN2D did not affect SBP. No salt sensitivity was observed in any of the genetically ablated mice. Future research will explore the effects of these subunits on renal hemodynamics.