A Micropuncture Study of the Net K Secretion in Thick Ascending Limb of Mice on a Low Na High K Diet

Abstract

Understanding the effect of a cardio‐ and reno‐protective low Na high K diet (LNaHK) on renal K handling is crucial to choosing diuretics and anti‐hypertensives for patients on such diets. We previously showed that furosemide, an inhibitor of the Na‐K‐Cl cotransporter (NKCC2) in the thick ascending limb (TAL), increased urinary K excretion (UKV) in mice on a control diet but decreased UKV in mice on LNaHK. We hypothesized that there is a net K secretion in the TAL of mice on LNaHK. Male C57BL/6 mice were given either a control diet or LNaHK for 7–14 days. Mice were anesthetized and received modified saline (140mM NaCl, 5mM KHCO3, 2% mannitol) intravenously. Free‐flow micropuncture was performed using K‐selective micro‐electrodes to measure the K concentration in the early distal tubule (EDT) before and after intravenous administration of vehicle (60μL 0.9% NaCl) or furosemide (60μL, 2mg/mL). Urine was collected via a bladder catheter. Urine Na concentration was measured by a flame photometer. Within 10 minutes of administration, furosemide increased [K] in the EDT of mice on a control diet (Δ = 1.88 ± 0.45 mM; N = 3) but decreased that of mice on LNaHK (Δ = −3.52 ± 0.85 mM; N = 4). Vehicle did not affect [K] in the EDT of mice on either diet. The increase in urinary Na excretion after furosemide was much greater in mice on LNaHK (1298 ± 354; N = 5 vs. 240 ± 56 nmol/min; N = 3). These results indicate that there is a net K secretion in TAL of mice on LNaHK, and it is associated with increased NKCC2 activity.Support or Funding InformationThis project was supported by NIDDK: F30 DK108456, RO1 DK092474.