scholarly journals Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

2015 ◽  
Vol 308 (9) ◽  
pp. F967-F980 ◽  
Author(s):  
Brendan C. Fry ◽  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Nitric Oxide ◽  
Interstitial Fluid ◽  
Rat Kidney ◽  
Kidney Injury ◽  
Renal Medulla ◽  
Urine Concentration ◽  
Renal Tubules ◽  
Vascular Bundles ◽  
Hospital Acquired ◽  
Radial Organization

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury.

scholarly journals Impact of nitric-oxide-mediated vasodilation and oxidative stress on renal medullary oxygenation: a modeling study

2016 ◽  
Vol 310 (3) ◽  
pp. F237-F247 ◽  
Author(s):  
Brendan C. Fry ◽  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Sodium Transport ◽  
Renal Medulla ◽  
Vascular Bundles ◽  
Active Sodium ◽  
Transport Efficiency ◽  
Active Sodium Transport ◽  
Vasa Recta ◽  
Radial Organization

The goal of this study was to investigate the effects of nitric oxide (NO)-mediated vasodilation in preventing medullary hypoxia, as well as the likely pathways by which superoxide (O2−) conversely enhances medullary hypoxia. To do so, we expanded a previously developed mathematical model of solute transport in the renal medulla that accounts for the reciprocal interactions among oxygen (O2), NO, and O2− to include the vasoactive effects of NO on medullary descending vasa recta. The model represents the radial organization of the vessels and tubules, centered around vascular bundles in the outer medulla and collecting ducts in the inner medulla. Model simulations suggest that NO helps to prevent medullary hypoxia both by inducing vasodilation of the descending vasa recta (thus increasing O2 supply) and by reducing the active sodium transport rate (thus reducing O2 consumption). That is, the vasodilative properties of NO significantly contribute to maintaining sufficient medullary oxygenation. The model further predicts that a reduction in tubular transport efficiency (i.e., the ratio of active sodium transport per O2 consumption) is the main factor by which increased O2− levels lead to hypoxia, whereas hyperfiltration is not a likely pathway to medullary hypoxia due to oxidative stress. Finally, our results suggest that further increasing the radial separation between vessels and tubules would reduce the diffusion of NO towards descending vasa recta in the inner medulla, thereby diminishing its vasoactive effects therein and reducing O2 delivery to the papillary tip.

scholarly journals Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

2012 ◽  
Vol 302 (5) ◽  
pp. F591-F605 ◽  
Author(s):  
Anita T. Layton ◽  
William H. Dantzler ◽  
Thomas L. Pannabecker
Keyword(s):  
Blood Flow ◽  
Interstitial Fluid ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Renal Medulla ◽  
Fluid Composition ◽  
Vascular Bundles ◽  
Vasa Recta ◽  
Countercurrent Exchange ◽  
Thin Limb

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data.

Expression of endothelial nitric oxide synthase in developing rat kidney

2005 ◽  
Vol 288 (4) ◽  
pp. F694-F702 ◽  
Author(s):  
Ki-Hwan Han ◽  
Jung-Mi Lim ◽  
Wan-Young Kim ◽  
Hyang Kim ◽  
Kirsten M. Madsen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Kidney Development ◽  
Early Stage ◽  
Rat Kidney ◽  
Immunoblot Analysis ◽  
Renal Hemodynamics ◽  
Vascular Bundles ◽  
Peritubular Capillaries ◽  
Endothelial Nitric Oxide

Endothelium-derived nitric oxide (NO) is synthesized within the developing kidney and may play a crucial role in the regulation of renal hemodynamics. The purpose of this study was to establish the expression and intrarenal localization of the NO-synthesizing enzyme endothelial NO synthase (eNOS) during kidney development. Rat kidneys from 14 ( E14)-, 16 ( E16)-, 18 ( E18)-, and 20-day-old ( E20) fetuses and 1 ( P1)-, 3 ( P3)-, 7 ( P7)-, 14 ( P14)-, and 21-day-old ( P21) pups were processed for immunocytochemical and immunoblot analysis. In fetal kidneys, expression of eNOS was first observed in the endothelial cells of the undifferentiated intrarenal capillary network at E14. At E16, strong eNOS immunoreactivity was observed in the endothelial cells of renal vesicles, S-shaped bodies (stage II glomeruli), and stage III glomeruli at the corticomedullary junction. At E18- 20, early-stage developing glomeruli located in the subcapsular region showed less strong eNOS immunoreactivity than those of E16. The eNOS-positive immature glomeruli were observed in the nephrogenic zone until 7 days after birth. In fetal kidneys, eNOS was also expressed in the medulla in the endothelial cells of the capillaries surrounding medullary collecting ducts. After birth, eNOS immunostaining gradually increased in the developing vascular bundles and peritubular capillaries in the medulla and was highest at P21. Surprisingly, eNOS was also expressed in proximal tubules, in the endocytic vacuolar apparatus, only at P1. The strong expression of eNOS in the early stages of developing glomeruli and vasculature suggests that eNOS may play a role in regulating renal hemodynamics of the immature kidney.

Effect of norepinephrine and acetylcholine on outer medullary descending vasa recta

1995 ◽  
Vol 269 (2) ◽  
pp. H710-H716 ◽  
Author(s):  
S. Yang ◽  
E. P. Silldorff ◽  
T. L. Pallone
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Cholinergic Innervation ◽  
Vascular Bundles ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasa Recta ◽  
Oxide Synthase

To examine their responsiveness to norepinephrine (NE) and acetylcholine (ACh), outer medullary descending vasa recta (OMDVR) have been dissected from vascular bundles of the rat and perfused in vitro. Abluminal application of NE produced graded vasoconstriction in a concentration range of 10(-9)-10(-6) M. When applied with NE, ACh at concentrations of 10(-8)-10(-5) M dilated NE-preconstricted OMDVR. In contrast, ACh applied in the absence of NE caused vasoconstriction. ACh-induced vasodilation was blocked by addition of the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA, 2 x 10(-4) M). L-NNA in the absence of ACh enhanced NE-induced vasoconstriction. Supraphysiological (10(-3) M) L-arginine (L-Arg) reversed the effects of L-NNA, and abluminal application of L-NNA alone resulted in OMDVR vasoconstriction. At concentrations of 10(-6)-10(-3) M, abluminal application of L-Arg produced graded vasodilation of NE-constricted OMDVR. These results suggest that adrenergic and cholinergic innervation could influence OMDVR vasomotor tone to modulate total and regional blood flow to the renal medulla. The data also favor a role for the activity of constitutively expressed nitric oxide synthase to modulate OMDVR vasoactivity.

scholarly journals Impact of renal medullary three-dimensional architecture on oxygen transport

2014 ◽  
Vol 307 (3) ◽  
pp. F263-F272 ◽  
Author(s):  
Brendan C. Fry ◽  
Aurélie Edwards ◽  
Ioannis Sgouralis ◽  
Anita T. Layton
Keyword(s):  
Oxygen Delivery ◽  
Interstitial Fluid ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Three Dimensional ◽  
Fluid Composition ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
The Impact

We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (Po2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial Po2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal Po2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the high metabolic requirements of the thick limbs and raises NaCl reabsorption.

Monoaminergic innervation of the rat kidney: a quantitative study

1990 ◽  
Vol 259 (3) ◽  
pp. F503-F511 ◽  
Author(s):  
L. Barajas ◽  
K. Powers
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Sympathetic Innervation ◽  
Renal Tubules ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
High Concentration ◽  
Renal Vasculature ◽  
Indirect Measure ◽  
Afferent Arterioles

The sympathetic innervation of the renal tubules and vasculature was characterized by measuring the overlap of accumulations of autoradiographic grains (AAGs) on these structures in autoradiograms of kidney sections from rats injected with tritiated norepinephrine. AAG overlap was used as an indirect measure of the innervation of those structures. The renal vasculature showed x 4.5 more AAG overlap than observed on renal tubules. The greatest amount of AAG overlap occurred on afferent arterioles, followed by efferent arterioles, interlobular arteries, cortical capillaries, arcuate arteries, and renal veins. High concentration of AAGs occurred along the vascular bundles of the outer stripe. In the tubular nephron the proximal tubule had the greatest amount of AAG overlap, followed by the cortical thick ascending limb of Henle, the connecting tubule, the distal convoluted tubule, and the collecting duct. It was found that afferent arterioles had significantly higher mean density of AAG overlap than efferent arterioles for the superficial, midcortical, and juxtamedullary (vascular bundles excluded) renal cortex. There was consistently more AAG perimeter facing the interstitium than overlapping the vasculature. These observations, together with the ultrastructural distribution of synaptic vesicles in varicosities, suggest that the interstitium might be an additional pathway of neurotransmitter access to the effector structures.

scholarly journals Ascending Vasa Recta Are Angiopoietin/Tie2-Dependent Lymphatic-Like Vessels

2017 ◽  
Vol 29 (4) ◽  
pp. 1097-1107 ◽  
Author(s):  
Yael Kenig-Kozlovsky ◽  
Rizaldy P. Scott ◽  
Tuncer Onay ◽  
Isabel Anna Carota ◽  
Benjamin R. Thomson ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Structural Integrity ◽  
Critical Role ◽  
Lymphatic Vessels ◽  
Renal Medulla ◽  
Vascular Bundles ◽  
Osmotic Gradient ◽  
Tyrosine Kinase 2 ◽  
Vasa Recta ◽  
Countercurrent Exchange

Urinary concentrating ability is central to mammalian water balance and depends on a medullary osmotic gradient generated by a countercurrent multiplication mechanism. Medullary hyperosmolarity is protected from washout by countercurrent exchange and efficient removal of interstitial fluid resorbed from the loop of Henle and collecting ducts. In most tissues, lymphatic vessels drain excess interstitial fluid back to the venous circulation. However, the renal medulla is devoid of classic lymphatics. Studies have suggested that the fenestrated ascending vasa recta (AVRs) drain the interstitial fluid in this location, but this function has not been conclusively shown. We report that late gestational deletion of the angiopoietin receptor endothelial tyrosine kinase 2 (Tie2) or both angiopoietin-1 and angiopoietin-2 prevents AVR formation in mice. The absence of AVR associated with rapid accumulation of fluid and cysts in the medullary interstitium, loss of medullary vascular bundles, and decreased urine concentrating ability. In transgenic reporter mice with normal angiopoietin-Tie2 signaling, medullary AVR exhibited an unusual hybrid endothelial phenotype, expressing lymphatic markers (prospero homeobox protein 1 and vascular endothelial growth factor receptor 3) as well as blood endothelial markers (CD34, endomucin, platelet endothelial cell adhesion molecule 1, and plasmalemmal vesicle–associated protein). Taken together, our data redefine the AVRs as Tie2 signaling–dependent specialized hybrid vessels and provide genetic evidence of the critical role of AVR in the countercurrent exchange mechanism and the structural integrity of the renal medulla.

Urinary concentrating ability: insights from comparative anatomy

1985 ◽  
Vol 249 (6) ◽  
pp. R643-R666 ◽  
Author(s):  
L. Bankir ◽  
C. de Rouffignac
Keyword(s):  
Water Conservation ◽  
Comparative Anatomy ◽  
Renal Medulla ◽  
Urine Concentration ◽  
Vascular Bundles ◽  
High Concentration ◽  
Morphological Adaptations ◽  
Time Required ◽  
Urinary Concentrating Ability ◽  
Coherent Picture

It appears difficult to build a coherent picture of the concentrating system of the mammalian renal medulla. This may be due to the diversity of the factors involved and to considerable interspecies differences. Several morphological adaptations that may be critical in the improvement of water conservation are described. They include variations in the length of the papilla, number of nephrons, percentage of long-looped nephrons, nephron heterogeneity, development of pelvic fornices, confluence of collecting ducts, vascular bundles in the inner stripe of the outer medulla, thin descending limb epithelium, and relative development of the three medullary zones. The organization of the medullary circulation is described; the medulla includes several functionally different compartments favoring preferential exchanges by the juxtaposition of certain tubules and vessels. This may improve the efficiency of certain recycling routes and hence the insulation of the different compartments. As discussed in section III, a better inner medullary insulation may be key, not (or not only) in achieving a high urine concentration but mainly in reducing the time required to reach this high concentration. This overview of the multiple interspecies variations in medullary organization underlines the importance, among other factors, of the inner stripe architecture and of the internephron differences in the process of urine concentration.

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