scholarly journals Nitric oxide and superoxide transport in a cross section of the rat outer medulla. II. Reciprocal interactions and tubulovascular cross talk

2010 ◽  
Vol 299 (3) ◽  
pp. F634-F647 ◽  
Author(s):  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Nitric Oxide ◽  
Cross Sections ◽  
Cross Talk ◽  
Three Dimensional ◽  
No Production ◽  
Outer Medulla ◽  
Nacl Transport ◽  
Hypoxic Conditions ◽  
Outer Stripe ◽  
Main Determinants

In a companion study (Edwards A and Layton AT. Am J Physiol Renal Physiol. doi:10.1152/ajprenal.00680.2009), we developed a mathematical model of nitric oxide (NO), superoxide (O2−), and total peroxynitrite (ONOO) transport in mid-outer stripe and mid-inner stripe cross sections of the rat outer medulla (OM). We examined how the three-dimensional architecture of the rat OM, together with low medullary oxygen tension (Po2), affects the distribution of NO, O2−, and ONOO in the rat OM. In the current study, we sought to determine generation rate and permeability values that are compatible with measurements of medullary NO concentrations and to assess the importance of tubulovascular cross talk and NO-O2− interactions under physiological conditions. Our results suggest that the main determinants of NO concentrations in the rat OM are the rate of vascular and tubular NO synthesis under hypoxic conditions, and the red blood cell (RBC) permeability to NO ( PNORBC). The lower the PNORBC, the lower the amount of NO that is scavenged by hemoglobin species, and the higher the extra-erythrocyte NO concentrations. In addition, our results indicate that basal endothelial NO production acts to significantly limit NaCl reabsorption across medullary thick ascending limbs and to sustain medullary perfusion, whereas basal epithelial NO production has a smaller impact on NaCl transport and a negligible effect on vascular tone. Our model also predicts that O2− consumption by NO significantly reduces medullary O2− concentrations, but that O2− , when present at subnanomolar concentrations, has a small impact on medullary NO bioavailability.

scholarly journals Modulation of outer medullary NaCl transport and oxygenation by nitric oxide and superoxide

2011 ◽  
Vol 301 (5) ◽  
pp. F979-F996 ◽  
Author(s):  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Nitric Oxide ◽  
Active Transport ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
Nacl Transport ◽  
Complex Interactions ◽  
Medullary Thick Ascending Limb ◽  
The Impact ◽  
Stimulation Of

We expanded our region-based model of water and solute exchanges in the rat outer medulla to incorporate the transport of nitric oxide (NO) and superoxide (O2−) and to examine the impact of NO-O2− interactions on medullary thick ascending limb (mTAL) NaCl reabsorption and oxygen (O2) consumption, under both physiological and pathological conditions. Our results suggest that NaCl transport and the concentrating capacity of the outer medulla are substantially modulated by basal levels of NO and O2−. Moreover, the effect of each solute on NaCl reabsorption cannot be considered in isolation, given the feedback loops resulting from three-way interactions between O2, NO, and O2−. Notwithstanding vasoactive effects, our model predicts that in the absence of O2−-mediated stimulation of NaCl active transport, the outer medullary concentrating capacity (evaluated as the collecting duct fluid osmolality at the outer-inner medullary junction) would be ∼40% lower. Conversely, without NO-induced inhibition of NaCl active transport, the outer medullary concentrating capacity would increase by ∼70%, but only if that anaerobic metabolism can provide up to half the maximal energy requirements of the outer medulla. The model suggests that in addition to scavenging NO, O2− modulates NO levels indirectly via its stimulation of mTAL metabolism, leading to reduction of O2 as a substrate for NO. When O2− levels are raised 10-fold, as in hypertensive animals, mTAL NaCl reabsorption is significantly enhanced, even as the inefficient use of O2 exacerbates hypoxia in the outer medulla. Conversely, an increase in tubular and vascular flows is predicted to substantially reduce mTAL NaCl reabsorption. In conclusion, our model suggests that the complex interactions between NO, O2−, and O2 significantly impact the O2 balance and NaCl reabsorption in the outer medulla.

Alternative oxidase is an important player in the regulation of nitric oxide levels under normoxic and hypoxic conditions in plants

2019 ◽  
Vol 70 (17) ◽  
pp. 4345-4354 ◽  
Author(s):  
Aprajita Kumari ◽  
Pradeep Kumar Pathak ◽  
Mallesham Bulle ◽  
Abir U Igamberdiev ◽  
Kapuganti Jagadis Gupta
Keyword(s):  
Nitric Oxide ◽  
Alternative Oxidase ◽  
Plant Mitochondria ◽  
No Production ◽  
Complex Iv ◽  
Increase Energy Efficiency ◽  
Hypoxic Conditions ◽  
Cytochrome Pathway ◽  
Important Player ◽  
Elicitor Treatments

Abstract Plant mitochondria possess two different pathways for electron transport from ubiquinol: the cytochrome pathway and the alternative oxidase (AOX) pathway. The AOX pathway plays an important role in stress tolerance and is induced by various metabolites and signals. Previously, several lines of evidence indicated that the AOX pathway prevents overproduction of superoxide and other reactive oxygen species. More recent evidence suggests that AOX also plays a role in regulation of nitric oxide (NO) production and signalling. The AOX pathway is induced under low phosphate, hypoxia, pathogen infections, and elicitor treatments. The induction of AOX under aerobic conditions in response to various stresses can reduce electron transfer through complexes III and IV and thus prevents the leakage of electrons to nitrite and the subsequent accumulation of NO. Excess NO under various stresses can inhibit complex IV; thus, the AOX pathway minimizes nitrite-dependent NO synthesis that would arise from enhanced electron leakage in the cytochrome pathway. By preventing NO generation, AOX can reduce peroxynitrite formation and tyrosine nitration. In contrast to its function under normoxia, AOX has a specific role under hypoxia, where AOX can facilitate nitrite-dependent NO production. This reaction drives the phytoglobin–NO cycle to increase energy efficiency under hypoxia.

scholarly journals Impact of nitric oxide-mediated vasodilation on outer medullary NaCl transport and oxygenation

2012 ◽  
Vol 303 (7) ◽  
pp. F907-F917 ◽  
Author(s):  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Supply And Demand ◽  
Vascular Bundles ◽  
Concentration Gradients ◽  
Outer Medulla ◽  
Nacl Transport ◽  
Reciprocal Interactions ◽  
Medullary Blood Flow ◽  
Vasa Recta

The present study aimed to elucidate the reciprocal interactions between oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on vascular and tubular function in the outer medulla. We expanded our region-based model of transport in the rat outer medulla (Edwards A, Layton AT. Am J Physiol Renal Physiol 301: F979–F996, 2011) to incorporate the effects of NO on descending vasa recta (DVR) diameter and blood flow. Our model predicts that the segregation of long DVR in the center of vascular bundles, away from tubular segments, gives rise to large radial NO concentration gradients that in turn result in differential regulation of vasoactivity in short and long DVR. The relative isolation of long DVR shields them from changes in the rate of NaCl reabsorption, and hence from changes in O2 requirements, by medullary thick ascending limbs (mTALs), thereby preserving O2 delivery to the inner medulla. The model also predicts that O2− can sufficiently decrease the bioavailability of NO in the interbundle region to affect the diameter of short DVR, suggesting that the experimentally observed effects of O2− on medullary blood flow may be at least partly mediated by NO. In addition, our results indicate that the tubulovascular cross talk of NO, that is, the diffusion of NO produced by mTAL epithelia toward adjacent DVR, helps to maintain blood flow and O2 supply to the interbundle region even under basal conditions. NO also acts to preserve local O2 availability by inhibiting the rate of active Na+ transport, thereby reducing the O2 requirements of mTALs. The dual regulation by NO of oxygen supply and demand is predicted to significantly attenuate the hypoxic effects of angiotensin II.

A model of nitric oxide tubulovascular cross talk in a renal outer medullary cross section

2007 ◽  
Vol 292 (2) ◽  
pp. F711-F722 ◽  
Author(s):  
Wensheng Zhang ◽  
Aurélie Edwards
Keyword(s):  
Blood Flow ◽  
Cross Section ◽  
Cross Talk ◽  
Vascular Bundle ◽  
Flow Distribution ◽  
Structural Heterogeneity ◽  
No Production ◽  
Vascular Bundles ◽  
Outer Medulla ◽  
Blood Flow Ratio

We developed a two-dimensional model of NO transport in a cross section of the inner stripe (IS) of the rat outer medulla to determine whether tubular and vascular generation of NO result in significant NO concentration (CNO) differences between the periphery and the center of vascular bundles and thereby affect medullary blood flow distribution. Following the approach of Layton and Layton (Layton AT, Layton HE. Am J Physiol Renal Physiol 289: F1346–F1366, 2006), the structural heterogeneity of the IS was incorporated in a representative unit consisting of four concentric regions centered on a vascular bundle. Our model suggests that the diffusion distance of NO in the interstitium is limited to a few micrometers. We predict that, under basal conditions, epithelial NO generation raises the average CNO in pericytes surrounding peripheral descending vasa recta (DVR) by a few nanomoles relative to that in pericytes surrounding central DVR. The short descending limbs and long ascending limbs are found to exert the greatest effect on CNO in pericytes; long descending limbs and short ascending limbs only have a moderate effect, whereas outer medullary collecting ducts, which are situated far from the vascular bundle center, do not affect pericyte CNO. Our results suggest that selective stimulation of epithelial NO production should significantly raise the periphery-to-center DVR diameter ratio, thereby increasing the outer medulla-to-inner medulla blood flow ratio. However, concomitant increases in epithelial superoxide (O2−) production would counteract this effect. This model confirms the importance of NO and O2− interactions in mediating tubulovascular cross talk.

scholarly journals Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Bin Li ◽  
Craig Skinner ◽  
Pablo R. Castello ◽  
Michiko Kato ◽  
Erin Easlon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Calorie Restriction ◽  
Mitochondrial Respiration ◽  
Molecular Mechanisms ◽  
Mitochondrial Respiratory Chain ◽  
Yeast Cells ◽  
Mitochondrial Activity ◽  
No Production ◽  
Hypoxic Conditions ◽  
Yeast Mutants

Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and studySaccharomyces cerevisiaemutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX). Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.

scholarly journals Enhanced Superoxide Production in Renal Outer Medulla of Dahl Salt-Sensitive Rats Reduces Nitric Oxide Tubular-Vascular Cross-Talk

Hypertension ◽  
2007 ◽  
Vol 49 (6) ◽  
pp. 1336-1341 ◽  
Author(s):  
Takefumi Mori ◽  
Paul M. O’Connor ◽  
Michiaki Abe ◽  
Allen W. Cowley
Keyword(s):  
Nitric Oxide ◽  
Cross Talk ◽  
Superoxide Production ◽  
Outer Medulla ◽  
Renal Outer Medulla

In vivo three-dimensional EPR imaging of nitric oxide production from isosorbide dinitrate in mice

1998 ◽  
Vol 274 (5) ◽  
pp. G857-G862 ◽  
Author(s):  
Satoshi Fujii ◽  
Yasuhiro Suzuki ◽  
Tetsuhiko Yoshimura ◽  
Hitoshi Kamada
Keyword(s):  
Nitric Oxide ◽  
Isosorbide Dinitrate ◽  
Epr Spectroscopy ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Water Soluble ◽  
Whole Body ◽  
No Production ◽  
Epr Signal

Recently, in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging have been widely used to investigate free radical distribution and metabolism in tissues, organs, and whole body of small animals. Endogenous nitric oxide (NO) is an attractive target of this method. In the present study, NO production from a nitrovasodilator, isosorbide dinitrate (ISDN), in live mice was investigated by in vivo EPR spectroscopy and imaging combined with the spin-trapping technique. A highly water-soluble Fe complex with N-(dithiocarboxy)sarcosine (DTCS) was used as an NO-trapping agent. Mice received [14N]ISDN, and the Fe-DTCS complex subcutaneously exhibited the characteristic triplet EPR signal of the NO adduct [14NO-Fe(DTCS)2]2−. Using [15N]ISDN instead of [14N]ISDN, we were able to observe that the doublet EPR signal stemmed from the15NO adduct, which directly demonstrated that NO was produced from ISDN. The three-dimensional EPR images of the upper abdomen of living mice showed that the NO adducts were distributed in the liver and the kidneys. This EPR image combined with the ex vivo EPR measurements of the blood suggested that NO production from ISDN occurred in the liver in this experimental condition.

Cross talk between prostacyclin and nitric oxide under shear in smooth muscle cell: role in monocyte adhesion

2001 ◽  
Vol 281 (1) ◽  
pp. H177-H182 ◽  
Author(s):  
Tomohiro Osanai ◽  
Noriyuki Akutsu ◽  
Norio Fujita ◽  
Takao Nakano ◽  
Koki Takahashi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Smooth Muscle ◽  
Cross Talk ◽  
No Synthase ◽  
Vascular Damage ◽  
No Production ◽  
A7r5 Cells ◽  
Cumulative Production ◽  
Prostacyclin Synthesis

We tested the hypothesis that at sites of vascular damage, vessel homeostasis is maintained through the cross talk of shear-induced production of prostacyclin and nitric oxide (NO) in vascular smooth muscle cells (VSMC). Confluent A7r5 cells derived from rat aortic VSMC and mesenteric VSMC were exposed to shear stress at 15 dyn/cm2 for 90 min with the use of a cone-plate device, and productions of prostacyclin and NO were examined. Shear stress increased cumulative production of prostacyclin by 3- to 3.5-fold and that of NO by 6- to 7.5-fold. Western blot analysis showed that inducible NO synthase protein was expressed after shear stress in both types of VSMC. Inhibition of NO synthase enhanced the shear-induced production of prostacyclin from 40 to 60%. Shear-induced production of NO was suppressed by 70% after treatment with 10−4 M of indomethacin. A7r5 cells adhesiveness for monocytes was suppressed by 50% after shear stress. This suppression was abolished by pretreatment with 10−4 M of indomethacin, whereas inhibition of NO synthase only minimally inhibited it. We conclude that there is a cross talk of shear-induced production of prostacyclin and NO in VSMC. At sites of vascular damage, prostacyclin synthesis may prevent monocyte adhesiveness for VSMC through the concomitant enhancement of NO production.

scholarly journals Three-dimensional reconstruction of the rat nephron

2014 ◽  
Vol 306 (6) ◽  
pp. F664-F671 ◽  
Author(s):  
Erik I. Christensen ◽  
Birgitte Grann ◽  
Inger B. Kristoffersen ◽  
Elisabeth Skriver ◽  
Jesper S. Thomsen ◽  
...  
Keyword(s):  
Structural Changes ◽  
Three Dimensional ◽  
Serial Sections ◽  
Mosaic Pattern ◽  
Outer Medulla ◽  
Short Loop ◽  
Collecting Ducts ◽  
Straight Tubules ◽  
Dimensional Reconstruction ◽  
Outer Stripe

This study gives a three-dimensional (3D) structural analysis of rat nephrons and their connections to collecting ducts. Approximately 4,500 2.5-μm-thick serial sections from the renal surface to the papillary tip were obtained from each of 3 kidneys of Wistar rats. Digital images were recorded and aligned into three image stacks and traced from image to image. Short-loop nephrons (SLNs), long-loop nephrons (LLNs), and collecting ducts (CDs) were reconstructed in 3D. We identified a well-defined boundary between the outer stripe and the inner stripe of the outer medulla corresponding to the transition of descending thick limbs to descending thin limbs and between the inner stripe and the inner medulla, i.e., the transition of ascending thin limbs into ascending thick limbs of LLNs. In all nephrons, a mosaic pattern of proximal tubule (PT) cells and descending thin limb (DTL) cells was observed at the transition between the PT and the DTL. The course of the LLNs revealed tortuous proximal “straight” tubules and winding of the DTLs within the outer half of the inner stripe. The localization of loop bends of SLNs in the inner stripe of the outer medulla and the bends of LLNs in the inner medulla reflected the localization of their glomeruli; i.e., the deeper the glomerulus, the deeper the bend. Each CD drained approximately three to six nephrons with a different pattern than previously established in mice. This information will provide a basis for evaluation of structural changes within nephrons as a result of physiological or pharmaceutical intervention.

scholarly journals Nitrogen isotopic fractionations during nitric oxide production in an agricultural soil

2020 ◽  
Author(s):  
Zhongjie Yu ◽  
Emily M. Elliott
Keyword(s):  
Nitric Oxide ◽  
Atmospheric Chemistry ◽  
Agricultural Soil ◽  
Agricultural Soils ◽  
Isotope Effects ◽  
Enzyme Level ◽  
Critical Role ◽  
N2o Emissions ◽  
No Production ◽  
Hypoxic Conditions

Abstract. Nitric oxide (NO) emissions from agricultural soils play a critical role in atmospheric chemistry and represent an important pathway for loss of reactive nitrogen (N) to the environment. With recent methodological advances, there is growing interest in the natural abundance N isotopic composition (δ15N) of soil-emitted NO and its utility in providing mechanistic information on soil NO dynamics. However, interpretation of soil δ15N-NO measurements has been impeded by the lack of constraints on the isotopic fractionations associated with NO production and consumption in relevant microbial and chemical reactions. In this study, anoxic (0 % O2), oxic (20 % O2), and hypoxic (0.5 % O2) incubations of an agricultural soil were conducted to quantify the net N isotope effects (15η) for NO production in denitrification, nitrification, and abiotic reactions of nitrite (NO2−) using a newly developed δ15N-NO analysis method. A sodium nitrate (NO3−) containing mass-independent oxygen-17 excess (quantified by a Δ17O notation) and three ammonium (NH4+) fertilizers spanning a δ15N gradient were used in soil incubations to help illuminate the reaction complexity underlying NO yields and δ15N dynamics in a heterogeneous soil environment. We found strong evidence for the prominent role of NO2− oxidation under anoxic conditions in controlling the apparent 15η for NO production from NO3− in denitrification (i.e., 49 to 60 ‰). These results highlight the importance of an under-recognized mechanism for the reversible enzyme NO2− oxidoreductase to control the N isotope distribution between the denitrification products. Through a Δ17O-based modeling of co-occurring denitrification and NO2− re-oxidation, the 15η for NO2− reduction to NO and NO reduction to nitrous oxide (N2O) were constrained to be 15 to 22 ‰ and −8 to 2 ‰, respectively. Production of NO in the oxic and hypoxic incubations was contributed by both NH4+ oxidation and NO3− consumption, with both processes having a significantly higher NO yield under O2 stress. Under both oxic and hypoxic conditions, NO production from NH4+ oxidation proceeded with a large 15η (i.e., 55 to 84 ‰) possibly due to expression of multiple enzyme-level isotopic fractionations during NH4+ oxidation to NO2− that involves NO as either a metabolic byproduct or an obligatory intermediate for NO2− production. Adding NO2− to sterilized soil triggered substantial NO production, with a relatively small 15η (19 ‰). Applying the estimated 15η values to a previous δ15N measurement of in situ soil NOx emission (NOx = NO + NO2) provided promising evidence for the potential of δ15N-NO measurements in revealing NO production pathways. Based on the observational and modeling constraints obtained in this study, we suggest that simultaneous δ15N-NO and δ15N-N2O measurements can lead to unprecedented insights into the sources of and processes controlling NO and N2O emissions from agricultural soils.

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