American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Jan 2006
A model of glucose transport and conversion to lactate in the renal medullary microcirculation.
In this study, we modeled mathematically the transport of glucose across renal medullary vasa recta and its conversion to lactate by anaerobic glycolysis. Uncertain parameter values were determined by seeking good agreement between predictions and experimental measurements of lactate generation rates, as well as glucose and lactate concentration ratios between the papilla and the corticomedullary junction; plausible kinetic rate constant and permeability values are summarized in tabular form. Our simulations indicate that countercurrent exchange of glucose from descending (DVR) to ascending vasa recta (AVR) in the outer medulla (OM) and upper inner medulla (IM) severely limits delivery to the deep inner medulla, thereby limiting medullary lactate generation. ⋯ The rate of lactate generation by anaerobic glycolysis of glucose supplied by blood from glomerular efferent arterioles is predicted to range from 2 to 8 nmol/s, in good agreement with lower estimates obtained from the literature (Bernanke D and Epstein FH. Am J Physiol 208: 541-545, 1965; Bartlett S, Espinal J, Janssens P, and Ross BD. Biochem J 219: 73-78, 1984).
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Am. J. Physiol. Renal Physiol. · Dec 2005
A region-based mathematical model of the urine concentrating mechanism in the rat outer medulla. II. Parameter sensitivity and tubular inhomogeneity.
In a companion study (Layton AT and Layton HE. Am J Physiol Renal Physiol 289: F1346-F1366, 2005), a region-based mathematical model was formulated for the urine concentrating mechanism (UCM) in the outer medulla (OM) of the rat kidney. In the present study, we quantified the sensitivity of that model to several structural assumptions, including the degree of regionalization and the degree of inclusion of short descending limbs (SDLs) in the vascular bundles of the inner stripe (IS). ⋯ These studies indicate that regionalization elevates the osmolality of the fluid delivered into the inner medulla via the collecting ducts; that model predictions are not significantly sensitive to boundary conditions; and that short vasa recta distribution and AVR permeabilities significantly impact concentrating capability. Moreover, we investigated, in the context of the UCM, the functional significance of several aspects of tubular segmentation and heterogeneity: SDL segments in the IS that are likely to be impermeable to water but highly permeable to urea; a prebend segment of SDLs that may be functionally like thick ascending limb (TAL); differing IS and outer stripe Na(+) active transport rates in TAL; and potential active urea secretion into the proximal straight tubules. Model calculations predict that these aspects of tubular of segmentation and heterogeneity generally enhance solute cycling or promote effective UCM function.
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Am. J. Physiol. Renal Physiol. · Dec 2005
A region-based mathematical model of the urine concentrating mechanism in the rat outer medulla. I. Formulation and base-case results.
We have developed a highly detailed mathematical model for the urine concentrating mechanism (UCM) of the rat kidney outer medulla (OM). The model simulates preferential interactions among tubules and vessels by representing four concentric regions that are centered on a vascular bundle; tubules and vessels, or fractions thereof, are assigned to anatomically appropriate regions. Model parameters, which are based on the experimental literature, include transepithelial transport properties of short descending limbs inferred from immunohistochemical localization studies. ⋯ The model exhibited solute exchange, cycling, and sequestration patterns (in tubules, vessels, and regions) that are generally consistent with predictions in the physiological literature, including significant urea addition from long ascending vasa recta to inner-stripe short descending limbs. In a companion study (Layton AT and Layton HE. Am J Physiol Renal Physiol 289: F1367-F1381, 2005), the impact of model assumptions, medullary anatomy, and tubular segmentation on the UCM was investigated by means of extensive parameter studies.
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Am. J. Physiol. Renal Physiol. · Dec 2005
Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases.
Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS (Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. ⋯ Both L-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by L-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.
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Am. J. Physiol. Renal Physiol. · Oct 2005
Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD.
Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat decreases AVP-induced water flow and releases PGE(2). We observed that dehydration of rats decreases the expression of P2Y2 receptor in inner medulla (IM) and P2Y2-R-mediated PGE(2) release by IMCD. Because circulating vasopressin (AVP) levels are increased in dehydrated condition, we examined whether chronic infusion of desmopressin (dDAVP) has a similar effect on the expression and activity of P2Y2-R. ⋯ Urinary PGE(2) metabolite excretion, however, did not change with dDAVP infusion. In conclusion, chronic dDAVP infusion decreases the expression and activity of P2Y2-R in IM. This may be due to a direct effect of dDAVP or dDAVP-induced increase in medullary tonicity.