OK cell sheets cultured on Transwell supports possess a leaky paracellular pathway resembling that of the proximal tubule epithelium in vivo.

Fluid and solute reabsorption by the proximal tubule is the result of both transcellular and paracellular flux. The role of transcellular transport has been extensively studied, but the importance of paracellular flux has not been as thoroughly investigated. The purpose of this review is to update concepts about the contribution of paracellular transport for reabsorption by the proximal tubule.

Abstract. Renal interstitial hydrostatic pressure (RIHP) is a link between increased arterial BP and natriuresis. The mechanism whereby increases in RIHP inhibits sodium and water transport across the mammalian proximal tubule epithelium may involve changes in flux across the tight junction of the proximal tubule. The purpose of this study was to determine the effects of increases in RIHP and inhibition of cyclooxygenase on paracellular backflux of an extracellular marker from the renal interstitium into the proximal tubule of the rat. During in vivo microperfusion of proximal tubules, the extracellular tracer of paracellular flux, lanthanum (La), was infused directly into the renal interstitium via a chronically implanted matrix. The net paracellular interstitium-to-lumen lanthanum backflux was measured before and after direct renal interstitial volume expansion (DRIVE) in the absence and presence of indomethacin. DRIVE significantly increased RIHP by 37% (⌬1.8 Ϯ 0.2 mmHg) and interstitium-to-lumen La backflux by 32% (⌬40.2 Ϯ 16.6 pg/min per mm), and it significantly decreased proximal reabsorption by 27% (⌬Ϫ7.7 Ϯ 3.8 nl/min; n ϭ 6). In indomethacin-treated rats (n ϭ 6), DRIVE again significantly increased RIHP by 40% (⌬1.9 Ϯ 0.2 mmHg), but it did not increase La backflux (⌬Ϫ39.0 Ϯ 24.4 pg/min per mm) or significantly decrease proximal reabsorption (⌬1.2 Ϯ 2.3 nl/ min). These results demonstrate that increased RIHP increases paracellular backflux of lanthanum from the renal interstitium to the proximal tubule lumen in association with decreases in proximal reabsorption. Furthermore, indomethacin blocks the effects of increased RIHP on proximal reabsorption and paracellular backflux of lanthanum through the intercellular tight junctions of the proximal tubule epithelium.Renal interstitial hydrostatic pressure (RIHP) is a link between increased arterial BP and natriuresis (1-3). The elevation of renal perfusion pressure results in increased RIHP. Increases in RIHP result in decreased proximal sodium reabsorption and an increase in fractional sodium excretion (4). Increases in RIHP during increases in mean arterial BP, during acute saline volume expansion and during direct renal interstitial volume expansion are associated with an inhibition of proximal tubule reabsorption and a natriuresis (1)(2)(3)(4)(5)(6)(7)(8). Although several studies have demonstrated a relationship between changes in RIHP and proximal tubule reabsorption, the mechanism whereby increases in RIHP inhibit sodium and water transport across the mammalian proximal tubule epithelium is unknown.Further studies have also examined the role of cyclooxygenase inhibition on proximal tubule sodium or water reabsorption during increases in RIHP. Selectively increasing RIHP by renal interstitial volume expansion was shown to increase PGE 2 excretion (9). Inhibition of cyclooxygenase by indomethacin administration during increases in renal perfusion pressure and during direct renal interstitial volume expansion attenuates the effects of increased RIHP on p...

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