WATER DEPRIVATION FUNCTIONALLY UPREGULATES NMDA RECEPTORS IN THE HYPOTHALMIC PVN TO SUPPORT RENAL SYMPATHETIC NERVE ACTIVITY (RSNA) AND ARTERIAL PRESSURE (AP).

Water deprivation activates pre‐autonomic neurons of the PVN and this depends largely on activation of ionotropic glutamate receptors. Since NMDAR are highly expressed in PVN, the effect of water deprivation on RSNA and AP responses to activation and blockade of NMDAR was determined. In anesthetized water replete (WR) and water deprived (WD) rats, unilateral PVN microinjection of NMDA (0, 50, 100, 200, 400 pmol, 50 nl) increased MAP and RSNA in a dose‐dependent manner. The Emax for RSNA responses in WD rats (94±15 % increase) was significantly greater (P=0.03) than in WR rats (47±7 % increase), suggesting that water deprivation may up‐regulate expression of NMDAR in the PVN as reported to occur in heart failure. Consistent with this possibility, RT‐QPCR revealed that NMDAR1 (NR1) subunit mRNA was increased in the PVN by 11% in WD rats (n=3) compared to WR rats (n=3). The role of NMDA receptors in supporting RSNA and MAP was examined by delivering the NMDAR antagonist AP5 unilaterally into the PVN at a dose of 3.0 nmol, which was predetermined to block maximal (200 pmol) NMDA‐evoked RSNA responses. AP5 alone significantly reduced RSNA (−17±1 %, p=0.01) and MAP (−20±5 mmHg, p=0.02) in WD rats (n=3). In contrast, AP5 in WR rats (n=4) reduced MAP only slightly (−7±2 mmHg, p= 0.04) and was without effect on RSNA (+8.8±5 %). We conclude that water deprivation increases the maximal RSNA response to PVN microinjection of NMDA (i.e., NMDA efficacy) and that tonic activation of NMDAR in the PVN supports RSNA and AP. Up‐regulation of NR1 subunit‐containing NMDAR may contribute to these observations. Support: HL071645 (GMT)