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 NaHCO(3) at 50 microl/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 hypertension increased medullary Na,K-ATPase activity from 20 +/- 3.5 to 27 +/- 6.4 micromol 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 activity. As chronic hypertension develops in the young spontaneously 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 hypertension contributes the driving force for activating TGF (by inhibition in the PT) and minimizes changes in distal sodium delivery (by activation in the TALH).