Abstract P381: Deletion of Na + /H + Exchanger 3 Selectively in the Proximal Tubule of the Kidney Augments Acute and Chronic Natriuretic Responses to Saline Volume Expansion in Mice

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 72; no. Suppl_1
• Main Authors: Li, Xiao C, Soleimani, Manoocher, Nugyen, Hoang T, Zhuo, Jia L
• Format: Journal Article
• Language: English
• Published: 01.09.2018
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.72.suppl_1.P381

Abstract only The Na + /H + exchanger 3 (NHE3), a ~85 kDa protein encoded by the SLC9A3 gene, plays a key role in mediating Na + reabsorption in the proximal tubule of the kidney and in maintaining blood pressure homeostasis. In the present study, we tested the hypothesis that deletion of NHE3 selectively in the proximal tubule of the kidney, but not globally, augments acute and chronic natriuretic responses to saline volume expansion in mice. Adult male wildtype ( Nhe3 +/+ ), global NHE3 knockout ( Nhe3 -/- ) and proximal tubule-specific NHE3 knockout mice (PT- Nhe3 -/- ) (n=8-13/group) were subject to acute saline administration of 10% body wt., i.p., or a 2% high salt diet for 2 weeks to determine and compare acute or chronic natriuretic responses. In response to 10% acute saline volume expansion, urinary Na + excretion increased 6.5 fold from basal 18.9 ± 5.0 μmol/3h to 122.2 ± 7.7 μmol/3h in wildtype mice ( p <0.01). By comparison, urinary Na + excretion increased 8.4 fold from basal 26.2 ± 3.9 μmol/3h to 206.5 ± 5.7 μmol/3h in PT- Nhe3 -/- mice ( p <0.01), whereas the natriuretic response increased 4.8 fold in Nhe3 -/- mice ( p <0.01). The differences in the natriuretic responses to acute saline expansion between Nhe3 +/+ , Nhe3 -/- and PT- Nhe3 -/- mice were statistically significant ( p <0.01). However, the diuretic response to acute water volume expansion (10% of body wt., i.p.) was not different between Nhe3 +/+ and PT- Nhe3 -/- mice ( n.s. ). In response to 2% NaCl diet for 2 weeks, 24 h urinary Na + excretion increased 19% in Nhe3 +/+ mice ( n.s. ), whereas the natriuretic response increased 43% in PT- Nhe3 -/- mice ( p <0.01). Interestingly, the natriuretic responses to 2% high salt diet were greater in adult female wildtype (Δ66%, p <0.01) and PT- Nhe3 -/- mice (Δ62%, p <0.01), respectively. By contrast, the natriuretic response to 2% high salt diet was significantly attenuated in global Nhe3 -/- mice ( p <0.01). These data suggest that the deletion of NHE3 selectively in the proximal tubule of the kidney, but not globally, augments the natriuretic responses to acute or chronic saline volume expansion in PT- Nhe3 -/- mice.