Requirement of aquaporin-1 for NaCl-driven water transport across descending vasa recta

Abstract

Deletion of AQP1 in mice results in diminished urinary concentrating ability, possibly related to reduced NaCl-and urea gradient-driven water transport across the outer medullary descending vasa recta (OMDVR). To quantify the role of AQP1 in OMDVR water transport, we measured osmotically driven water permeability in vitro in microperfused OMDVR from wild-type, AQP1 heterozygous, and AQP1 knockout mice. OMDVR diameters in AQP1 -/-mice were 1.9-fold greater than in AQP1 +/+ mice. Osmotic water permeability (P f ) in response to a 200 mM NaCl gradient (bath > lumen) was reduced about 2-fold in AQP1 +/-mice and by more than 50-fold in AQP1 -/-mice. P f increased from 1015 to 2527 µm/s in AQP1 +/+ mice and from 22 to 1104 µm/s in AQP1 -/-mice when a raffinose rather than an NaCl gradient was used. This information, together with p-chloromercuribenzenesulfonate inhibition measurements, suggests that nearly all NaCl-driven water transport occurs by a transcellular route through AQP1, whereas raffinose-driven water transport also involves a parallel, AQP1-independent, mercurial-insensitive pathway. Interestingly, urea was also able to drive water movement across the AQP1-independent pathway. Diffusional permeabilities to small hydrophilic solutes were comparable in AQP1 +/+ and AQP1 -/-mice but higher than those previously measured in rats. In a mathematical model of the medullary microcirculation, deletion of AQP1 resulted in diminished concentrating ability due to enhancement of medullary blood flow, partially accounting for the observed urine-concentrating defect.

Aquaporin‐1 expression in the chick embryo chorioallantoic membrane

“…Our data concerning the immunoreactivity of the endothelium of CAM blood vessels to AQP1 suggest that also at this level AQP1 might be implicated in governing the water pathway through the endothelium, as has been established in the descending vasa recta (Pallone et al, 2000) and in microvessels of alveolar and distal airways (Bai et al, 1999). Moreover, in AQP1 knockout mice it has been shown that AQP1 provides a quantitatively important "exclusive water pathway" for osmotically induced water movement across the capillary endothelium (Yang et al, 1999), representing 10 -45% of the total transcellular hydraulic permeability of the microvascular wall (Renkin and Curry, 1982;Wolf and Watson, 1989).…”

“…It is also expressed in endothelial cells of nonfenestrated capillaries (Nielsen et al, 1993) and human arteries (Shanahan et al, 1999), and its mRNA has been found in vascular smooth muscle cells (VSMCs) of human aorta, arteries, and capillaries, as well as in a subset of VSMCs of human atherosclerotic plaques (Shanahan et al, 1999). The involvement of AQP1 in transendothelial water transport of nonfenestrated endothelium has been shown in descending vasa recta (Nielsen et al, 1993;Pallone et al, 1994Pallone et al, , 2000 and in peritoneal capillaries (Devust et al, 1998). Its tissue distribution, developmental expression pattern, and biophysical properties have been largely elucidated (Bondy et al, 1993;Agre et al, 1994).…”

Functions of aquaporins in the eye

“…Mice lacking AQP1 show reduced water permeability in proximal tubule with impaired near-isosmolar fluid absorption (Schnermann et al, 1998). AQP1 deletion also reduces water permeability of the thin descending limb of Henle (Chou et al, 1999) and vasa recta microvessels (Pallone et al, 2000), which prevents the generation of a hyperosmolar medullary interstitium. Deletion or mutation of AQPs 2-4 reduces collecting duct water permeability, preventing osmotic equilibration between the renal interstitium and urinary fluid in the collecting duct lumen.…”

Dissecting the Roles of Aquaporins in Renal Pathophysiology Using Transgenic Mice

“…As predicted by this model, a substantial ~40 mOsm transepithelial osmotic gradient was found in end proximal tubule fluid of AQP1 null mice, much greater than that of ~10 mOsm in wildtype mice (19). AQP1 also provides the major route for transepithelial water permeability in thin descending limb of Henle (TDLH) and outer medullary descending vasa recta (OMDVR) (20). These results indicate that AQP1 is the principal water channel in TDLH, and support the conclusion that osmotic equilibration in TDLH plays a key role in the renal countercurrent concentrating mechanism.…”

“…These results indicate that AQP1 is the principal water channel in TDLH, and support the conclusion that osmotic equilibration in TDLH plays a key role in the renal countercurrent concentrating mechanism. Analysis of AQP1-dependent water transport in OMDVR in response to gradients of NaCl vs. raffinose indicated that solutes larger than NaCl are able to drive water movement through both AQP1 and an AQP1-independent, mercurialinsensitive pathway that may involve paracellular transport (20). The primary interpretation of microperfusion and micropuncture data is that AQP1 deletion impairs urinary concentrating ability by impairing near-isosmolar fluid absorption by proximal tubule and by interfering with the normally hypertonic medullary interstitium generated by countercurrent multiplication and exchange.…”