Renal responses to short term non‐pressor AngII ± intrarenal RAS blockade in rats

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Long term (14d) AngII infusion augments intrarenal AngII production and raises blood pressure; ACE inhibition (ACEi) blunts both responses. This study aimed to determine 1) the renal responses to a short term (3 d) non‐pressor dose of AngII and 2) whether the responses were blunted by ACEi treatment implicating local AngII production. Male Sprague‐Dawley rats were infused via osmotic minipumps with either vehicle (control) or AngII (200 ng/kg/min) ± the ACEi enalapril (30 mg/kg/day in drinking water). There were no significant differences in body weight gain, overnight urine volume, or urinary Na and K excretion among the groups. Abundance of renal transporters was determined by quantitative immunoblot, and normalized to control values, defined as 1.0. Control AngII AngII + enalapril Cortex NHE3 total 1.00 ± 0.05 1.51 ± 0.14* 1.37 ± 0.02* NHE3‐P 1.00 ± 0.07 1.37 ± 0.09 1.45 ± 0.13* NKCC total 1.00 ± 0.09 1.70 ± 0.23* 1.57 ± 0.11 NKCC‐P 1.00 ± 0.17 1.96 ± 0.20* 2.13 ± 0.17* NCC total 1.00 ± 0.05 1.33 ± 0.08* 1.12 ± 0.03 NCCpS71 1.00 ± 0.07 1.29 ± 0.09* 1.01 ± 0.04 SPAK total 1.00 ± 0.19 2.71 ± 0.55* 2.87 ± 0.40* Medulla NKCC total 1.00 ± 0.04 0.70 ± 0.05* 0.75 ± 0.07* NKCC‐P 1.00 ± 0.03 0.82 ± 0.11 1.22 ± 0.28 SPAK total 1.00 ± 0.02 0.99 ± 0.06 0.98 ± 0.03 p<0.05 vs. control. Conclusion1) 3 d AngII infusion increases cortical NHE3, NKCC, NCC and SPAK while decreasing medullary NKCC abundance. 2) Blocking intrarenal RAS with enalapril blunted the effects of AngII infusion on NCC total, NCCp, and NKCC indicating these are early targets of intrarenal RAS stimulation and, thus, intrarenal ACE inhibition. NIH R01 DK 083785.