Abstract
Chronic AngII infusion raises blood pressure (BP) in mice which depends on renal AngII receptors (AT1R). AngII is anti‐natriuretic while high BP is natriuretic.Aim 1To determine how AngII infusion affects Na+ transporter abundance and phosphorylation (by immunoblot of homogenates). AngII infusion (1 μg/kg/min x 14d) increases systolic BP ~30 mmHg. Versus sham infused (=1.0), AngII decreased total NHE3 to 0.7±0.1, NHE3‐P (at Ser552) to 0.8±0.1 without altering NHE3 ‐P/total ratio. NaPi2 and myosin VI were unchanged. Distal convoluted tubule (DCT) total NCC increased to 2.2±0.3, NCC‐P (at Thr60) to 5.4 ± 1.6 and NCC‐P/total ratio to 2.2±0.5 fold.Aim 2To determine the role of proximal tubule (PT) AT1R in regulation of Na+ transporters in mice lacking PT AT1R (KO). BP decreased 10mmHg in KO vs. WT and baseline expression of NHE3, NaPi2, and NCC were unchanged in KO vs. WT. AngII infusion increased BP 20mmHg less than in WT. AngII infusion in KO decreased: total NHE3 to 0.55±0.1, NHE3‐P to 0.66±0.1 (no change in ‐P/total NHE3 ratio), myosin VI to 0.56±0.1, NaPi2 to 0.64±0.1. NCC total and NCC‐P were unchanged in the AngII infused KO.Conclusions1) increased NCC contributes to AngII induced high BP while decreased PT NHE3 compensates for high BP in WT, 2) AngII dependent increase in NCC depends on PT AT1R, and 3) the removal of PT AT1R facilitates pressure natriuresis by further decreasing PT transporters during AngII infusion.
Published Version
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