Decreased renal perfusion rapidly increases plasma membrane Na-K-ATPase in rat cortex by an angiotensin II-dependent mechanism (original) (raw)

2009, American Journal of Physiology-renal Physiology

To understand how rapid changes in blood pressure can regulate Na-K-ATPase in the kidney cortex, we tested the hypothesis that a short-term (5 min) decrease in renal perfusion pressure will increase the amount of Na-K-ATPase in the plasma membranes by an angiotensin II-dependent mechanism. The abdominal aorta of anesthetized Sprague-Dawley rats was constricted with a ligature between the renal arteries, and pressure was monitored on either side during acute constriction. Left renal perfusion pressure was reduced to 70 Ϯ 1 mmHg (n ϭ 6), whereas right renal perfusion pressure was 112 Ϯ 4 mmHg. In control (nonconstricted) rats (n ϭ 5), pressure to both kidneys was similar at 119 Ϯ 6 mmHg. After 5 min of reduced perfusion, femoral venous samples were taken for plasma renin activity (PRA) and the kidneys excised. The cortex was dissected, minced, sieved, and biotinylated. Lower perfusion left kidneys showed a 41% increase (P Ͻ 0.003) in the amount of Na-K-ATPase in the plasma membrane compared with right kidneys. In controls, there was no difference in cell surface Na-K-ATPase between left and right kidneys (P ϭ 0.47). PRA was 57% higher in experimental animals compared with controls. To test the role of angiotensin II in mediating the increase in Na-K-ATPase, we repeated the experiments (n ϭ 6) in rats treated with ramiprilat. When angiotensin-converting enzyme was inhibited, the cell surface Na-K-ATPase of the two kidneys was equal (P ϭ0.46). These results confirm our hypothesis: rapid changes in blood pressure regulate trafficking of Na-K-ATPase in the kidney cortex. ouabain; sodium; blood pressure; renin THE PROXIMAL TUBULE REABSORBS approximately two-thirds of the filtered sodium, which contributes to the control of plasma blood volume and the regulation of blood pressure. The Na-K-ATPase is an active transport protein in the basolateral membrane that is widely recognized as playing a key role in sodium reabsorption. The hormone dopamine inhibits (4) and angiotensin II (ANG II) directly stimulates the short-term (Յ15 min) activity of the Na-K-ATPase (1, 5, 6, 7, 21), which eventually affects blood pressure. In opossum kidney cells, a cell culture model of proximal tubules, which express the ␣ 1-subunit of the rat kidney Na-K-ATPase, the short-term stimulation of Na-K-ATPase activity by ANG II is mediated by the AT 1 receptor, which stimulates PKC that in turn increases the phosphorylation of Na-K-ATPase and thereby triggers increased trafficking of Na-K-ATPase to the plasma membrane (5, 6).