Acute saline expansion increases nephron filtration and distal flow rate but maintains tubuloglomerular feedback responsiveness: role of adenosine A1 receptors

Temporal adaptation of tubuloglomerular feedback (TGF) permits readjustment of the relationship of nephron filtration rate [single nephron glomerular filtration rate (SNGFR)] and early distal tubular flow rate (V ED ) while maintaining TGF responsiveness. We used closed-loop assessment of TGF in hydropenia and after acute saline volume expansion (SE; 10% body wt over 1 h) to determine whether 1 ) temporal adaptation of TGF occurs, 2 ) adenosine A 1 receptors (A 1 R) mediate TGF responsiveness, and 3 ) inhibition of TGF affects SNGFR, V ED , or urinary excretion under these conditions. SNGFR was evaluated in Fromter-Wistar rats by micropuncture in 1 ) early distal tubules (ambient flow at macula densa), 2 ) recollected from early distal tubules while 12 nl/min isotonic fluid was added to late proximal tubule (increased flow to macula densa), and 3 ) from proximal tubules of same nephrons (zero flow to macula densa). SE increased both ambient SNGFR and V ED compared with hydropenia, whereas TGF responsiveness (proximal-distal difference in SNGFR, distal SNGFR response to adding fluid to proximal tubule) was maintained, demonstrating TGF adaptation. A 1 R blockade completely inhibited TGF responsiveness during SE and made V ED more susceptible to perturbation in proximal tubular flow, but did not alter ambient SNGFR or V ED . Greater urinary excretion of fluid and Na + with A 1 R blockade may reflect additional effects on the distal nephron in hydropenia and SE. In conclusion, A 1 R-independent mechanisms adjust SNGFR and V ED to higher values after SE, which facilitates fluid and Na + excretion. Concurrently, TGF adapts and stabilizes early distal delivery at the new setpoint in an A 1 R-dependent mechanism.