Na,K-ATPase in isolated nephron segments in rats with experimental heart failure

Abstract

To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (U(Na)V), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, U(Na)V was 0.66 ± 0.04 (mean ± SEM) μeq/min, and aldosterone was 18.4 ± 3.5 ng%. Na,K-ATPase activity (in 10-11 mol/mm/min) was 28.4 ± 1.1 in the proximal convoluted tubule, 23.3 ± 1.0 in the proximal straight tubule, 37.4 ± 1.9 in the medullary thick ascending limb, 40.2 ± 1.9 in the cortical thick ascending limb, 43.2 ± 2.2 in the distal convoluted tubule, and 20.5 ± 0.9 in the cortical collecting duct. For the group with moderate heart failure, U(Na)V was 0.35 ± 0.02 (p < 0.001 versus control), and aldosterone was 15.9 ± 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 ± 3.1 (p < 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 ± 1.2 (p < 0.005 versus control). For the group with severe heart failure, U(Na)V was 0.029 ± 0.016 (p < 0.001 versus control), and aldosterone was 186.0 ± 14.8 (p < 0.001 versus control). Na,K-ATPase activity increased in the proximal convoluted tubule and proximal straight tubule to 36.6 ± 1.5 and 40.7 ± 1.8, respectively (p < 0.001 versus control for both). Na,K-ATPase activity decreased in the medullary and cortical thick ascending limbs and distal convoluted tubule to 21.9 ± 3.4, 23 ± 1.4, and 24.0 ± 1.5, respectively (p < 0.001 versus control for all). Angiotensin II (10-10 M) increased Na,K-ATPase activity in proximal convoluted and straight tubules from control values of 27.1 ± 0.4 and 23.3 ± 1.7 to 34.4 ± 1.8 (p < 0.001) and 36.0 ± 1.6 (p < 0.001), respectively. These results show that, in rats with heart failure, Na,K-ATPase varies with the severity of Na+ retention. In severe heart failure the increased Na,K-ATPase activity in the proximal nephron may be related to increased angiotensin II levels.