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

Abstract

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 (VED) 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 A1 receptors (A1R) mediate TGF responsiveness, and 3) inhibition of TGF affects SNGFR, VED, 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 VED 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. A1R blockade completely inhibited TGF responsiveness during SE and made VED more susceptible to perturbation in proximal tubular flow, but did not alter ambient SNGFR or VED. Greater urinary excretion of fluid and Na+ with A1R blockade may reflect additional effects on the distal nephron in hydropenia and SE. In conclusion, A1R-independent mechanisms adjust SNGFR and VED 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 A1R-dependent mechanism.