Dietary protein affects urea transport across rat urothelia

Abstract

Spector DA, Deng J, Stewart KJ. Dietary protein affects urea transport across rat urothelia. Am J Physiol Renal Physiol 303: F944-F953, 2012. First published July 25, 2012 doi:10.1152/ajprenal.00238.2012.-Recent evidence suggests that regulated solute transport occurs across mammalian lower urinary tract epithelia (urothelia). To study the effects of dietary protein on net urothelial transport of urea, creatinine, and water, we used an in vivo rat bladder model designed to mimic physiological conditions. We placed groups of rats on 3-wk diets differing only by protein content (40,18,6, and 2%) and instilled 0.3 ml of collected urine in the isolated bladder of anesthetized rats. After 1 h dwell, retrieved urine volumes were unchanged, but mean urea nitrogen (UN) and creatinine concentrations fell 17 and 4%, respectively, indicating transurothelial urea and creatinine reabsorption. The fall in UN (but not creatinine) concentration was greatest in high protein (40%) rats, 584 mg/dl, and progressively less in rats receiving lower protein content: 18% diet, 224 mg/dl; 6% diet, 135 mg/dl; and 2% diet, 87 mg/dl. The quantity of urea reabsorbed was directly related to a urine factor, likely the concentration of urea in the instilled urine. In contrast, the percentage of instilled urea reabsorbed was greater in the two dietary groups receiving the lowest protein (26 and 23%) than in those receiving higher protein (11 and 9%), suggesting the possibility that a bladder/urothelial factor, also affected by dietary protein, may have altered bladder permeability. These findings demonstrate significant regulated urea transport across the urothelium, resulting in alteration of urine excreted by the kidneys, and add to the growing evidence that the lower urinary tract may play an unappreciated role in mammalian solute homeostasis.solute transport across bladder epithelia; urothelial creatinine transport; regulation of urothelial urea transport ALTHOUGH MAMMALIAN LOWER URINARY tract functions primarily as a short-term transit and storage vehicle for urine made by the kidneys (13), recent data demonstrate that mammalian urothelia (the epithelial cell lining of the urinary tract from renal pelvis to proximal urethra) is a surprisingly dynamic and complex tissue that may play an unappreciated role in water and solute homeostasis (35)(36)(37)(38)(39) reviewed in Ref. 22). While the urothelial permeability barriers, thought to reside in the apical membrane of the large "umbrella" cells lining the urinary tract lumens, the tight junction (TJ) between those cells, and the adherent overlying urinary glycosaminoglycans (GAG) layer (18,19,22,24,48), have been shown in vitro to have low permeability to water, urea, and ions (9,25,28), there are a number of physiological factors that might be expected to promote (even) passive diffusion of water and solutes across these barriers, including the large urinary tract lumenal surface area, long storage time of urine, enormous and changing concentration gradients for water, solutes, and ions, and ...

Dietary restriction in moderately obese rats improves body size and glucose handling without the renal and hepatic alterations observed with a high-protein diet

“…Interestingly, the lower weight gain in HP compared with NP in OP rats used in the current study occurred despite a higher feed intake in these rats. A similar higher feed intake with HP feeding was observed previously in a study with healthy male Wistar rats (Aparicio et al 2013), although numerous studies have shown decreased feed intake in response to HP (Bensaid et al 2002) or no effect of HP on feed intake (Spector et al 2012). Increased leucine intake as a result of the HP diet is suggested to play a role in controlling satiety (Cota et al 2006), although such an effect was not observed in some studies (Nairizi et al 2009;Noatsch et al 2011).…”

Aquaporin‐2 plays an important role in water transportation through the bladder wall in rats

“…Therefore, it was hypothesized that some channels in the urothelium function in the condition of full‐filled (distended) bladder because AQPs transport water only. Urea, sodium, and chlorine move across rat urothelial cells, but the underlying mechanism has not been elucidated. The epithelial sodium channel (ENaC) mediates sodium transport across the apical membrane of the urinary bladder epithelium .…”

Hydration status affects sodium, potassium, and chloride transport across rat urothelia

“…Since DFVs contain ENaC and likely other transporter proteins, DFV cycling may promote changes in ion and solute transport, and indeed functional studies in Ussing chambers have shown that stretching of the umbrella cells resulted in increased sodium reabsorption (via ENaC) and secretion of potassium and chloride (43). Furthermore, as we have previously speculated, DFV cycling may promote net ion/solute transport directly by incorporating urinary constituents into endocytic vesicles and cytoplasmic ions and solutes into exocytic vesicles (35). Little is known about the possible effect(s) of bladder stretch on the GAGs layer lining the bladder lumen or the permeability characteristics of the umbrella cell tight junctions.…”

“…3, 21, and 24). Recent work indicates that one such function might be to alter the concentration of urinary constituents as a result of secretion of urothelial solutes into urine or the converse, reabsorption of urinary solutes across urothelium and into deeper bladder tissues, thereby suggesting a role in urinary tract tissue and/or whole body water and solute homeostasis (34,35,39,43). Such transport is unexpected given the evidence from Ussing chamber studies that mammalian urothelia possess exceptionally low permeabilities to urinary constit-uents (5,13,17,28).…”

“…To study mammalian urothelial water and solute transport and building on models utilized in past studies, we recently developed and reported on an in vivo, in situ bladder model which closely mimics physiological conditions in rats (34,35).…”