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Hypertension (Dallas, Tex. : 1979) Jan 1997This study examined the production of nitric oxide (NO) in the renal cortex and medulla through the use of an in vivo microdialysis technique. Oxyhemoglobin (OxyHb) at a...
This study examined the production of nitric oxide (NO) in the renal cortex and medulla through the use of an in vivo microdialysis technique. Oxyhemoglobin (OxyHb) at a concentration of 3 mumol/L was perfused through the dialysis system to trap tissue NO. Methemoglobin (MetHb), which was formed by NO oxidation of OxyHb in the dialysate, was spectrophotometrically assayed at 401 nm. Because the oxidation of OxyHb to produce MetHb is stoichiometric with NO, the production of NO can be determined by the rate of MetHb formation. We found that NO concentration was significantly higher (P < .05) in the medulla (57.1 +/- 5.57 nmol/L, n = 10) than in the cortex (31.2 +/- 5.7 nmol/L, n = 9). The minimal detectable NO level of this assay is approximately 10 nmol/L. Intravenous infusion of L-arginine (3 mg/kg per minute) for 30 minutes produced a twofold to three fold increase in cortical and medullary NO; NG-nitro-L-arginine methyl ester (L-NAME) (10 micrograms/kg per minute) decreased NO by 33% in the renal cortex and by 46.5% in the renal medulla. We have also compared under the same conditions the degradation products of NO, nitrite, and nitrate in the renal cortex and medulla using in vivo microdialysis combined with microtiter plate colorimetry. Nitrite/nitrate concentration was significantly higher (P < .05) in the medulla (2.7 +/- 0.6 mumol/L, n = 4) than in the cortex (2.1 +/- 0.2 mumol/L, n = 4). Infusion of L-arginine increased cortical and medullary nitrite/nitrate by 65% and 39%, respectively. L-NAME reduced cortical and medullary nitrite/nitrate by 18% and 23%, respectively. The results indicate that the OxyHb-NO microdialysis trapping technique is a highly sensitive in situ method for detecting regional tissue NO concentration and changes in the NO synthase activity in the kidney. These studies have shown that NO concentration is higher in medullary tissue than in the cortex.
Topics: Animals; Kidney Cortex; Kidney Medulla; Methemoglobin; Microdialysis; Nitric Oxide; Nitroprusside; Rats; Rats, Sprague-Dawley; Superoxide Dismutase
PubMed: 9039101
DOI: 10.1161/01.hyp.29.1.194 -
The Journal of Pharmacology and... Sep 2012Medullipin has been proposed to be an antihypertensive lipid hormone released from the renal medulla in response to increased arterial pressure and renal medullary blood...
Medullipin has been proposed to be an antihypertensive lipid hormone released from the renal medulla in response to increased arterial pressure and renal medullary blood flow. Because anandamide (AEA) possesses characteristics of this purported hormone, the present study tested the hypothesis that AEA or one of its metabolites represents medullipin. AEA was demonstrated to be enriched in the kidney medulla compared with cortex. Western blotting and enzymatic analyses of renal cortical and medullary microsomes revealed opposite patterns of enrichment of two AEA-metabolizing enzymes, with fatty acid amide hydrolase higher in the renal cortex and cyclooxygenase-2 (COX-2) higher in the renal medulla. In COX-2 reactions with renal medullary microsomes, prostamide E2, the ethanolamide of prostaglandin E₂, was the major product detected. Intramedullarily infused AEA dose-dependently increased urine volume and sodium and potassium excretion (15-60 nmol/kg/min) but had little effect on mean arterial pressure (MAP). The renal excretory effects of AEA were blocked by intravenous infusion of celecoxib (0.1 μg/kg/min), a selective COX-2 inhibitor, suggesting the involvement of a prostamide intermediate. Plasma kinetic analysis revealed longer elimination half-lives for AEA and prostamide E2 compared with prostaglandin E₂. Intravenous prostamide E2 reduced MAP and increased renal blood flow (RBF), actions opposite to those of angiotensin II. Coinfusion of prostamide E2 inhibited angiotensin II effects on MAP and RBF. These results suggest that AEA and/or its prostamide metabolites in the renal medulla may represent medullipin and function as a regulator of body fluid and MAP.
Topics: Angiotensin II; Animals; Arachidonic Acids; Arterial Pressure; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Endocannabinoids; Glycerides; Kidney Cortex; Kidney Medulla; Kinetics; Lipids; Male; Mice; Mice, Inbred C57BL; Microsomes; Polyunsaturated Alkamides; Potassium; Pyrazoles; Renal Circulation; Sodium; Sulfonamides
PubMed: 22685343
DOI: 10.1124/jpet.112.196451 -
Physiological Reviews Oct 1991Sorbitol, inositol, GPC, and betaine are the predominant organic osmolytes in renal medullary cells. They protect the cells from harmful effects of the high interstitial... (Review)
Review
Sorbitol, inositol, GPC, and betaine are the predominant organic osmolytes in renal medullary cells. They protect the cells from harmful effects of the high interstitial NaCl and urea concentrations that occur normally in the renal medulla with operation of the urinary concentrating mechanism. Their levels correlate with extracellular NaCl concentration and, in the case of GPC, also with urea. Sorbitol is synthesized from glucose in a reaction catalyzed by aldose reductase. Inositol and betaine are transported into the cell. Glycerophosphorylcholine synthesis is dependent on choline. The transcription of aldose reductase and the transport of betaine and inositol are regulated, dependent on the degree of hypertonicity. Normal organic osmolyte regulation contributes to the survival and growth of medullary cells in their hyperosmolal environment, and defective regulation can damage them.
Topics: Animals; Betaine; Glycerylphosphorylcholine; Humans; Inositol; Kidney Medulla; Osmolar Concentration; Sorbitol; Taurine
PubMed: 1924548
DOI: 10.1152/physrev.1991.71.4.1081 -
Annals of the New York Academy of... Apr 1994
Review
Topics: Animals; Humans; Hypoxia; Indomethacin; Kidney; Kidney Medulla; Oxygen; Partial Pressure; Regional Blood Flow
PubMed: 8185253
DOI: No ID Found -
American Journal of Physiology. Renal... Feb 2003Perfusion of the renal medulla plays an important role in salt and water balance. Pericytes are smooth muscle-like cells that impart contractile function to descending... (Review)
Review
Perfusion of the renal medulla plays an important role in salt and water balance. Pericytes are smooth muscle-like cells that impart contractile function to descending vasa recta (DVR), the arteriolar segments that supply the medulla with blood flow. DVR contraction by ANG II is mediated by depolarization resulting from an increase in plasma membrane Cl(-) conductance that secondarily gates voltage-activated Ca(2+) entry. In this respect, DVR may differ from other parts of the efferent microcirculation of the kidney. Elevation of extracellular K(+) constricts DVR to a lesser degree than ANG II or endothelin-1, implying that other events, in addition to membrane depolarization, are needed to maximize vasoconstriction. DVR endothelial cytoplasmic Ca(2+) is increased by bradykinin, a response that is inhibited by ANG II. ANG II inhibition of endothelial Ca(2+) signaling might serve to regulate the site of origin of vasodilatory paracrine agents generated in the vicinity of outer medullary vascular bundles. In the hydropenic kidney, DVR plasma equilibrates with the interstitium both by diffusion and through water efflux across aquaporin-1. That process is predicted to optimize urinary concentration by lowering blood flow to the inner medulla. To optimize urea trapping, DVR endothelia express the UT-B facilitated urea transporter. These and other features show that vasa recta have physiological mechanisms specific to their role in the renal medulla.
Topics: Animals; Arterioles; Blood Vessels; Humans; Kidney Medulla; Microcirculation; Renal Circulation; Vasomotor System
PubMed: 12529271
DOI: 10.1152/ajprenal.00304.2002 -
Hypertension (Dallas, Tex. : 1979) Jan 2000Recent studies have shown that the heme oxygenase (HO) product, carbon monoxide (CO), induces vasodilation and that inhibition of HO produces a sustained hypertension in...
Recent studies have shown that the heme oxygenase (HO) product, carbon monoxide (CO), induces vasodilation and that inhibition of HO produces a sustained hypertension in rats. Given the importance of renal medullary blood flow (MBF) in the long-term control of arterial blood pressure, we hypothesized that the HO/CO system may play an important role in maintaining the constancy of blood flow to the renal medulla, which in turn contributes to the antihypertensive effects of the renal medulla. To test this hypothesis, we first determined the expression of 2 isoforms of HO (HO-1 and HO-2) in the different kidney regions. By Northern blot analyses, the abundance of both isozyme mRNAs was found highest in the renal inner medulla and lowest in the renal cortex. The transcripts for HO-1 in the renal outer medulla and inner medulla were 2.5 and 3.7 times that expressed in the renal cortex and those for HO-2 in the outer medulla and inner medulla were 1.3 and 1.6 times that expressed in the renal cortex, respectively. Western blot analyses of both enzymes showed the same expression pattern in these kidney regions as the mRNAs. To determine the role that HO plays in the control of renal MBF, we examined the effect of the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) on cortical blood flow and MBF in anesthetized rats. ZnDPBG was given by renal medullary interstitial infusion, and cortical blood flow and MBF were measured by laser Doppler flowmetry. Renal medullary interstitial infusion of ZnDPBG at a dose of 60 nmol/kg per minute produced a 31% decrease in MBF over a period of 60 minutes as measured by laser Doppler flow signal (0.62+/-0.02 vs 0.43+/-0.04 V in control vs ZnDPBG). With the use of an in vivo microdialysis technique, ZnDPBG was found to significantly reduce renal medullary cGMP concentrations when infused into the renal medullary interstitial space. These results suggest that both HO-1 and HO-2 are highly expressed in the renal medulla, that HO and its products play an important role in maintaining the constancy of blood flow to the renal medulla, and that cGMP may mediate the vasodilator effect of HO products in the renal medullary circulation.
Topics: Animals; Blood Pressure; Blotting, Northern; Blotting, Western; Cyclic GMP; Fluorescent Dyes; Gene Expression Regulation, Enzymologic; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Kidney Cortex; Kidney Medulla; Laser-Doppler Flowmetry; Male; Microdialysis; Oxygen; RNA, Messenger; Rats; Rats, Sprague-Dawley; Renal Circulation; Triglycerides; Ultrasonography; Zinc
PubMed: 10642322
DOI: 10.1161/01.hyp.35.1.342 -
Frontiers in Bioscience : a Journal and... Jun 2000Blood flow to the renal medulla is supplied through descending vasa recta (DVR), which are derived from the efferent arterioles of juxtamedullary glomeruli. In addition... (Review)
Review
Blood flow to the renal medulla is supplied through descending vasa recta (DVR), which are derived from the efferent arterioles of juxtamedullary glomeruli. In addition to their role as conduits for blood flow, it is accepted that the vasa recta are countercurrent exchangers. That process, however, involves events which are more complicated than paracellular diffusive exchange of NaCl and urea. Urea transport in DVR is accommodated through the combined expression of endothelial and erythrocyte facilitated carriers while transport of water involves solute driven efflux across water channels. Unlike DVR, which have a continuous endothelium, ascending vasa recta (AVR) are fenestrated with a very high hydraulic conductivity. Transport of water in AVR is probably governed by transmural hydraulic and oncotic pressure gradients. The parallel arrangement of DVR in outer medullary vascular bundles coupled with their capacity for vasomotion implies a role for regulation of the regional distribution of blood flow within the medulla The importance of the latter process in the urinary concentrating mechanism and the exchange of nutrients and O2 is poorly defined. The large number of hormones and autacoids that influence DVR vasomotion, however, suggests that DVR have evolved to optimize the functions of the renal medulla.
Topics: Animals; Kidney Medulla; Microcirculation; Renal Circulation
PubMed: 10833463
DOI: 10.2741/edwards -
Biological Trace Element Research Oct 2019In the body, disorders in the composition and concentration of trace elements, including copper, can lead to the development of various alterations that may result in...
In the body, disorders in the composition and concentration of trace elements, including copper, can lead to the development of various alterations that may result in incorrect functioning of the kidneys. Data on the concentrations of copper in human kidneys are discussed; however, little is known about the concentration of trace elements within rejected renal grafts and kidneys with tumor lesions. The aim of our study was to compare the copper concentration between cancerous kidneys and rejected renal grafts with the division on renal cortex and renal medulla. Material consisted of kidneys from patients hospitalized at the Department of Urology and General Surgery and Transplantation of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, north-western Poland. The study material consisted of kidneys with tumor lesions (n = 33), and renal grafts (n = 10), obtained from patients belongs to the north-western areas of Poland. The examination was performed using ICP-AES method. Regarding the pathological kidneys, excluding grafts, the concentration of Cu in the renal cortex was 52% higher than in medullary region and the difference between the compared concentrations was statistically confirmed (p < 0.05). Taking into account renal grafts, the concentration of Cu in the medulla was slightly lower than in the cortex (less than 3%). In summary, copper in rejected and cancerous kidneys tends to accumulate in higher amount in the renal cortex than medulla, what can be explained by the fact that renal corpuscles, where the first phase of filtration is performed, are located only in the cortical region of the kidney. Furthermore, renal grafts accumulate significantly less copper than kidneys with neoplastic changes, what could have been caused by immunosuppressive medicines used by the graft recipients. The lower copper concentration in renal grafts could be a consequence of the altered immune system, including inflammatory process or/and non-immune mechanisms. Additionally, cancerous and non-cancerous kidneys exhibit different perfusion rate in renal glomeruli, what can finally lead to disparity in chemical elements concentration, including copper.
Topics: Adult; Aged; Copper; Female; Humans; Kidney; Kidney Medulla; Kidney Neoplasms; Kidney Transplantation; Male; Middle Aged
PubMed: 30645698
DOI: 10.1007/s12011-018-1621-6 -
Hypertension (Dallas, Tex. : 1979) Feb 2001The present study characterized the biochemical pathways responsible for superoxide (O(2)(-.)) production in different regions of the rat kidney and determined the role...
The present study characterized the biochemical pathways responsible for superoxide (O(2)(-.)) production in different regions of the rat kidney and determined the role of O(2)(-.)in the control of renal medullary blood flow (MBF) and renal function. By use of dihydroethidium/DNA fluorescence spectrometry with microtiter plates, the production of O(2)(-. )was monitored when tissue homogenate from different kidney regions was incubated with substrates for the major O(2)(-.)-producing enzymes, such as NADH/NADPH oxidase, xanthine oxidase, and mitochondrial respiratory chain enzymes. The production of O(2)(-. )via NADH oxidase was greater (P<0.05) in the renal cortex and outer medulla (OM) than in the papilla. The mitochondrial enzyme activity for O(2)(-.)production was higher (P<0.05) in the OM than in the cortex and papilla. Compared with NADH oxidase and mitochondrial enzymes, xanthine oxidase and NADPH oxidase produced much less O(2)(-. )in the kidney under this condition. Overall, the renal OM exhibited the greatest enzyme activities for O(2)(-.)production. In anesthetized rats, renal medullary interstitial infusion of a superoxide dismutase inhibitor, diethyldithiocarbamate, markedly decreased renal MBF and sodium excretion. Diethyldithiocarbamate (5 mg/kg per minute by renal medullary interstitial infusion [RI]) reduced the renal medullary laser-Doppler flow signal from 0.6+/-0.04 to 0.4+/-0.03 V, a reduction of 33%, and both urine flow and sodium excretion decreased by 49%. In contrast, a membrane-permeable superoxide dismutase mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (TEMPOL, 30 micromol/kg per minute RI) increased MBF and sodium excretion by 34% and 69%, respectively. These effects of TEMPOL on renal MBF and sodium excretion were not altered by pretreatment with N(G)-nitro-L-arginine methyl ester (10 microgram/kg per minute RI). We conclude that (1) renal medullary O(2)(-. )is primarily produced in the renal OM; (2) both NADH oxidase and mitochondrial enzymes are responsible for the O(2)(-.)production in this kidney region; and (3) O(2)(-. )exerts a tonic regulatory action on renal MBF.
Topics: Animals; Cyclic N-Oxides; Ditiocarb; Electron Transport; Enzyme Inhibitors; Kidney Cortex; Kidney Medulla; Male; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Natriuresis; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Renal Circulation; Spectrometry, Fluorescence; Spin Labels; Superoxide Dismutase; Superoxides
PubMed: 11230333
DOI: 10.1161/01.hyp.37.2.547 -
Journal of the American Society of... Oct 2018Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure...
BACKGROUND
Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity.
METHODS
To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation.
RESULTS
Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise.
CONCLUSIONS
Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.
Topics: Adult; Blood Flow Velocity; Exercise; Female; Hand Strength; Healthy Volunteers; Humans; Kidney Cortex; Kidney Medulla; Magnetic Resonance Imaging; Male; Middle Aged; Oxygen; Renal Artery; Renal Circulation; Sympathetic Nervous System; Young Adult
PubMed: 30206141
DOI: 10.1681/ASN.2018030272