Abstract P011: Novel Roles Of Global, Intestinal, And Kidney Proximal Tubule Sodium And Hydrogen Exchanger 3 In Angiotensin Ii-induced Hypertension

The present study used global ( Nhe3 -/- ), kidney-selective (tg Nhe3 -/- ), and proximal tubule-specific Na + /H + exchanger 3 (NHE3)-deficient mice (PT- Nhe3 -/- ) to test the hypothesis that NHE3 is required for the full development of angiotensin II (Ang II)-induced hypertension in mice. Four groups of adult male, age-matched wild-type (WT), global Nhe3 -/- , kidney-selective tg Nhe3 -/- and proximal tubule-specific Nhe3 -/- mice were infused with: a) saline; b) Ang II (10 pmol/min, i.v.); Ang II via an osmotic minipump for 2 weeks (1.5 mg/kg/day, i.p.); or treated with Ang II and losartan concurrently for 2 weeks (20 mg/kg/day, p.o.). Under basal conditions, global Nhe3 -/- , kidney-selective tg Nhe3 -/- and proximal tubule-specific Nhe3 -/- mice all showed significantly lower systolic, diastolic, and mean arterial pressure than wild-type mice (~15 ± 3 mmHg, P Nhe3 -/- and kidney-selective tg Nhe3 -/- mice was associated with abnormal intestinal structures, diarrhea, increased 24 h fecal Na + excretion, and salt wasting ( P + excretion between wild-type and PT- Nhe3 -/- mice. PT- Nhe3 -/- mice showed significant diuretic and natriuretic responses compared with wild-type mice ( P P Nhe3 -/- , kidney-selective tg Nhe3 -/- , and PT- Nhe3 -/- mice ( P Nhe3 -/- , tgNhe3 -/- , and PT- Nhe3 -/- mice, compared with wild-type mice ( P Nhe3 -/- , tg Nhe3 -/- , and PT- Nhe3 -/- mice (p