Regulation of proximal tubule sodium/hydrogen antiporter with chronic volume contraction

We developed a model of volume contraction in rabbits by using a furosemide /low- salt diet to follow changes, if any, in proximal tubule Na+/H+ exchan ger 3 (NHE3) mRNA and brush-border protein. The rabbits' plasma renin, aldo sterone, and urine sodium content confirmed the volume-contracted state. RN ase protection assays demonstrated increases in treated-animal NHE3 mRNA as a percentage of control with 172 +/- 23, 154 +/- 15, 153 +/- 14, and 141 /- 7 (SE)%( P< 0.05) at 1, 5, 10, and 31 days, respectively. Western analys is of brush-border membrane with NHE3 antibody revealed increased immunorea ctivity in treated animals as a percentage of control with 120 +/- 30, 190 +/- 59, 307 +/- 72, and 427 +/- 41% (P< 0.05) at 1, 5, 10, and 31 days, res pectively. There was no significant difference in serum potassium, bicarbon ate, and cortisol in control vs. experimental animals. These data suggest t hat there is chronic upregulation of NHE3 in the volume-contracted state.