Increased tubuloglomerular feed‐back mediated suppression of glomerular filtration during acute volume expansion in rats.

Abstract

SUMMARY1. Volume expansion is currently believed to change the intrinsic properties of the juxtaglomerular apparatus such that the sensitivity of the tubuloglomerular feedback (TGF) mechanism is reduced, thus allowing glomerular filtration rate, and hence salt and water excretion, to rise. Recent studies conflict with this view and indeed the older literature reveals that the rise in glomerular filtration rate (GFR) under these conditions is far more modest than would be expected if TGF control were eliminated.2. To investigate this problem, TGF control of filtration rate was examined by measuring single-nephron glomerular filtration rate (SNGFR) during loop of Henle perfusion at varying rates in rats under control conditions, after acute, moderate (4% of body weight), iso-oncotic volume expansion and in rats treated with antibodies to atrial natriuretic peptide (ANP) prior to the acute volume expansion.3. With TGF control of filtration interrupted by filtrate collection from the proximal tubule, SNGFR in the expanded rats was massively increased compared with controls, although SNGFR measured in the distal tubule, and hence with TGF control intact, was only modestly increased, as was whole-kidney filtration rate.Loop perfusion at increasing rates up to 30 nl min-' progressively decreased SNGFR in controls, and in the expanded rats the range over which control was exerted extended up to 60-80 nl min-'. For changes in loop flow around the spontaneous operating point, the sensitivity of the TGF mechanism, defined as A SNGFR/A loop flow, was similar in both groups. Treatment of rats with ANP antibodies prior to volume expansion substantially blunted the changes in renal salt and water excretion and the increase in SNGFR seen in the absence of loop perfusion.4. These results are not consistent with a diminution of TGF function after

The macula densa is worth its salt

“…As a consequence of this shift, GFR in the post-benzolamide phase was actually higher than in control. The hyperfiltration and the pattern of TGF resetting caused by benzolamide are strikingly similar to those seen previously during acute extracellular volume expansion, another state in which the macula densa is exposed for some time to an increase in NaCl concentration (13,17). Interestingly, the benzolamideinduced TGF resetting outlasted the actual duration of the high perfusion stimulus.…”

Comparison of cystometric methods in female rats

“…Intravascular infusion of saline at 0.080 ml/min was used to provoke maximal physiologic diuresis in response to subacute fluid loading. 20 Infusion and data collection were continued until several voids had occurred, typically requiring 5-6 hr. Bladder pressure data was not collected as no intravesical catheters were placed in this group.…”

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

“…These studies at least suggested that decreased sensitivity of TGF may contribute to the efficient off-loading or excretion of Na ϩ and water following SE. However, other studies concluded that TGF persisted after more modest SE, actually acting to limit the increase in GFR (7,8).…”

“…Several prior studies have examined TGF characteristics during acute volume loading, but with somewhat different techniques and goals in mind (4,5,7,8,18,22,39). For the most part, the earlier studies utilized open-loop techniques by perfusing the macula densa segments from the late proximal tubule and assessing SNGFR or stop-flow pressure responses.…”

“…Acute saline volume expansion (SE) is another condition in which temporal adaptation of TGF is likely to occur. However, certain conditions impair the ability to undergo TGF temporal adaptation and include 1) nitric oxide synthase (NOS)-1 inhibition (29) and 2) cyclooxygenase-2 inhibition (11), and there may be other conditions in which TGF resetting or temporal adaptation is impaired or absent.Studies in the literature have suggested that acute SE requires modifications in TGF that include both 1) temporal adaptation of the relationship of SNGR and distal delivery rates and/or 2) diminished sensitivity or responsiveness of TGF (4,5,7,8,18,22,39). These predictions reflect some logic since the combination of both TGF adaptation and suppression of TGF should facilitate NaCl excretion by lifting the TGFmediated constraints on SNGFR/glomerular filtration rate (GFR), thereby increasing the delivery to the distal tubule.…”