Dependence of Saline-Induced Natriuresis upon Exposure of the Kidney to the Physical Effects of Extracellular Fluid Volume Expansion

Abstract

A B S T R A C T In many previous studies, the natriuresis induced by saline loading has been demonstrated to persist even though glomerular filtration rate (GFR) has been decreased to below pre-expansion levels by a reduction in renal artery pressure. In such studies, however, the kidney has been exposed to the effects of volume expansion for varying periods of time before renal artery pressure was controlled. The present experiments were designed to evaluate whether this period of exposure induces critical changes in intrarenal factors that are responsible for the natriuresis.Experiments were carried out in rats, in which renal artery pressure was decreased to 70 mm Hg either at the onset of saline loading (immediate clamping experiments) or after 45 min of saline loading had elapsed (delayed clamping experiments). In the delayed clamping experiments, consonant with previous studies, mean sodium excretion, 3.2 ,seq/min, remained markedly increased above control, despite a reduction in GFR to 91% of the hydropenic control value. In contrast, when renal artery pressure was comparably reduced at the onset of saline loading mean sodium excretion was only trivially increased, 0.4 These results exclude an important role for either a circulating hormone or a reduction in plasma oncotic pressure in the natriuretic response to saline loading, and indicate that intrarenal factors are the critical determinants of the natriuresis. We have used the difference in response to saline loading in the immediate and delayed clamping experiments to evaluate the role of two intrarenal factors, interstitial hydrostatic pressure and renal plasma flow. Interstitial pressure changes were estimated from changes in tubular pressure and diameter by using the in situ compliance characteristics of the tubules. In a group of rats saline loaded without aortic clamping, interstitial pressure increased by 4-5 mm Hg and renal plasma flow increased by 2.5 ml/min. During the period of reduced renal artery pressure, however, neither interstitial pressure nor renal plasma flow was detectably increased above control in either the immediate or the delayed clamping experiments.The only noteworthy difference between the experiments in which a natriuresis occurred (unclamped and delayed clamping studies) and the experiments in which no natriuresis occurred is that in the former group the kidney was at least transiently exposed both to an increase in renal plasma flow and interstitial pressure.

Mechanism of Inhibition of Proximal Tubule Fluid Reabsorption after Exposure of the Rat Kidney to the Physical Effects of Expansion of Extracellular Fluid Volume

“…As shown in Fig. 2 (2) showed in rats that the natriuresis induced by saline loading was largely abolished when renal perfusion pressure was reduced to -70 mm Hg immediately before (EC), but not after (LC), the volume load. These findings, which have since been confirmed by others (3)(4)(5)(6), were also duplicated in the present study.…”

“…In view of these observations, the authors of these various studies have suggested that intrarenal, rather than plasma compositional or circulating humoral, factors were primarily responsible for these differing reabsorptive responses to early vs. late clamping. Moreover, insofar as systemic protein concentration (4) and filtration fraction (2) were affected equally by early and late clamping, these studies might also be taken as evidence against a role for postglomerular oncotic pressure as a major determinant of these differing sodium reabsorptive responses. Without an evalua-tion of the remaining transcapillary Starling forces, however, a meaningful assessment of the role of peritubular physical factors under these conditions is not possible.…”

“…where Pc is estimated3 to be 0.5 x (PE + PCi)- 2 Since distal convoluted tubules of superficial nephrons are also perfused with surface peritubular capillaries, APR undoubtedly underestimates true peritubular capillary fluid uptake in absolute terms. In view of the small amount of reabsorption by cortical distal convolutions (t-Y5% of filtered load), however, the magnitude of this underestimation is quite small.…”

“…More recently, Fitzgibbons et al (2) noted that whereas natriuresis persisted in saline-loaded rats despite reduction in renal perfusion pressure (late clamp), this natriuretic response to volume expansion was markedly blunted when renal perfusion pressure was reduced before the administration of the saline load (early clamp). This finding has since been confirmed by others (3)(4)(5)(6).…”

Role of Renal Interstitial Hydrostatic Pressure in the Blunted Natriuretic Response to Saline Loading in the Piglet

“…Acute saline VE in th e ad ult results in signi ficant increases in RIHP and sodium excretion (6). When th e rise in RIHP is prevented from in creasing during VE in the adult, the increase in sodium excretion is signific antly attenuated (7,8). Furthermore , direct increa ses in RIHP comparable to the RIHP measured during VE result in significa nt increases in sod iu m excretion (9).…”