Downstream Shift in Sodium Pump Activity along the Nephron during Acute Hypertension

Acute hypertension rapidly inhibits proximal tubule (PT) Na,K-ATPase activity and sodium reabsorption 30 to 40%, increasing sodium and volume delivery to the thick ascending loop of Henle (TALH) and macula densa, providing the error signal for tubuloglomerular feedback. The hypothesis was tested in rats that an acute increase in sodium and volume delivery to the TALH would acutely increase outer medulla Na,K-ATPase activity. Flow to the TALH was increased by either (1) elevating BP (102 to 160 mmHg) for 5 min by constricting arteries (hypertension) or ( 2) inhibiting PT sodium and volume reabsorption with the carbonic anhydrase inhibitor benzolamide: 2 mg/kg in 300 mM NaHCO3 at 50 l/min for 5 to 7 min. Both stimuli increased urine output and lithium clearance three- to four-fold and increased basolateral Na,K- ATPase activity about 40%. In homogenates, acute hyperten- sion increased medullary Na,K-ATPase activity from 20 3.5 to 27 6.4 mol Pi/mg protein per h while decreasing renal cortex activity from 10.9 0.9 to 6.5 0.7. Hypertension and benzolamide also doubled medullary alkaline phosphatase ac- tivity. As chronic hypertension develops in the young sponta- neously hypertensive rat, medullary Na,K-ATPase activity similarly increases. In conclusion, there is a rapid activation of medullary Na,K-ATPase activity during acute hypertension that can be explained by the increase in sodium and volume flow to the region independent of hypertension. That is, the glomerulotubular balance response in the loop of Henle is accompanied by increased Na,K-ATPase activity. The rapid, downstream shift in Na,K-ATPase activity during acute hyper- tension contributes the driving force for activating TGF (by inhibition in the PT) and minimizes changes in distal sodium delivery (by activation in the TALH). Arterial pressure fluctuates in normal animals, but highly ef- ficient autoregulation prevents any measurable changes in re- nal blood flow (RBF) or GFR. This autoregulation is mediated in part by tubuloglomerular feedback (TGF), specifically, an increase in afferent arteriolar resistance in response to in- creased delivery of NaCl to the macula densa. In other words, normal fluctuations in BP provoke fluctuations in NaCl reab- sorption proximal to the macula densa, which change afferent arteriolar resistance to normalize RBF and GFR (1,2). Chou and Marsh (3,4) addressed the conceptual difficulty in understanding how acute hypertension could lead to increased NaCl delivery to the macula densa in the absence of a change in GFR or NaCl filtration rate. Using micropuncture of rat renal tubules, they discovered that acute hypertension rapidly inhibits proximal tubule (PT) volume reabsorption, increasing end PT fluid velocity 40%, which could provide the error signal for TGF, and verified that the response occurred in the absence of a measurable change in GFR. An acute decrease in