Acute saline expansion increases nephron filtration and distal flow rate but maintains tubuloglomerular feedback responsiveness: role of adenosine A(1) receptors - PubMed (original) (raw)

Acute saline expansion increases nephron filtration and distal flow rate but maintains tubuloglomerular feedback responsiveness: role of adenosine A(1) receptors

Roland C Blantz et al. Am J Physiol Renal Physiol. 2012.

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 (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.

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Figures

Fig. 1.

Fig. 1.

Closed-loop analysis of tubuloglomerular feedback (TGF) activity_._ The sequence of collections is described with initial evaluation of single nephron glomerular filtration rate (SNGFR) by early distal tubule collection (1) and a repeat collection (3), whereas 12 nl/min fluid is added to freely flowing late proximal tubule (2) and then a collection from late proximal tubule at zero flow to the distal tubule (4).

Fig. 2.

Fig. 2.

Assessment of the TGF status by examining SNGFR at various levels of early distal tubular flow rate using closed-loop analysis in hydropenia, saline expansion, and during treatment with the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). SNGFR in “Proximal” collections reflects zero flow, “Distal” is SNGFR at ambient flow rates, and “Distal plus 12 nl/min” during addition of fluid to freely flowing late proximal tubule of the same nephron. These data examine the vasodilatory and vasoconstrictor elements of TGF and find the system intact in hydropenia and during saline expansion and inhibited by adenosine A1 receptor (A1R) blockade; the inhibition by A1R blockade of the vasoconstrictor arm of TGF to adding tubular fluid was blunted in hydropenia. NS, not significant. *P < 0.05 vs. distal.

Fig. 3.

Fig. 3.

Early distal tubular flow rates (VED) and fractional fluid reabsorption up to the early distal tubule (FR) in hydropenia, saline expansion, and during treatment with the A1R antagonist DPCPX. VED and FR are depicted during basal conditions and when 12 nl/min fluid were added to late proximal tubular flow. Adding fluid to the late proximal tubule induced similar modest increases in VED in hydropenia and with saline expansion. When TGF is inhibited during saline expansion with DPCPX treatment, VED increases markedly more (*P < 0.05 vs. basal; #P < 0.05 vs. change in response from untreated hydropenia and saline expansion alone).

Fig. 4.

Fig. 4.

VED as a function of SNGFR in hydropenia, saline expansion, and during treatment with the A1R antagonist DPCPX. Depicted are measurements from freely flowing early distal tubules. The linear regression coefficients (_r_2) and the significance of the linear regression are listed. A positive linear relationship was observed between SNGFR and VED in all groups except during DPCPX in hydropenia; A1R tone appeared to enhance tubular fluid reabsorption upstream of the early distal tubule, in particular, in nephrons with low tubular loads (SNGFR) in hydropenia.

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