(Hypertension. 1997;29:194.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
Nitric Oxide in Renal Cortex and Medulla
An In Vivo Microdialysis Study
From the Department of Physiology, Medical College of Wisconsin, Milwaukee.
Correspondence to Ai-Ping Zou, MD, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226
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Abstract |
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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 µmol/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
10 nmol/L. Intravenous infusion of L-arginine (3 mg/kg per minute) for 30 minutes produced a twofold to threefold increase in cortical and medullary NO; NG-nitro-L-arginine methyl ester (L-NAME) (10 µg/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 µmol/L, n=4) than in the cortex (2.1±0.2 µmol/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.
Key Words: spectrophotometry • rats • nitric oxide • microdialysis • kidney
Abbreviations: L-NAME = NG-nitro-L-arginine methyl ester • MetHb = methemoglobin • NO = nitric oxide • NOS = nitric oxide synthase • OxyHb = oxyhemoglobin • PBS = phosphate-buffered saline • SNP = sodium nitroprusside • SOD = superoxide dismutase
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Introduction |
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There is evidence that NO formation may play an important role in the regulation of renal function.1–4 Recently, we have found that endogenous NO participates in the control of renal medullary blood flow, water and sodium excretion, and arterial blood pressure. Chronic inhibition of endogenous NO in the renal medulla markedly decreased medullary blood flow and sodium excretion and consequently resulted in a rise of arterial blood pressure in rats.5,6 Measurement of cGMP indicated that NO production in the renal medulla is greater than in the renal cortex,7–9 and Western blot analysis demonstrated a greater expression of NOS in the renal medulla.10 However, direct measurement of NO concentration in various regions of the kidney has not been carried out, and because NO is the final effector stimulus in this pathway, it is important to be able to measure its concentration in the regions of functional interest. Here we report the use of an in vivo microdialysis hemoglobintrapping technique to determine NO levels in the renal medulla and cortex and to examine the effect of L-arginine and its analogue on renal cortical and medullary levels of NO.
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Methods |
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In Vivo Microdialysis
In vivo microdialysis studies were performed as described by Baranowski and Westenfelder.11 Briefly, the rats (Sprague-Dawley; weight, 290 to 310 g) were anesthetized with ketamine (30 mg/kg IM) and Inactin (40 mg/kg IP), and body temperature was maintained at 37°C. The trachea, femoral artery, and vein were cannulated. We exposed and immobilized the left kidney by placing it dorsal side up in a kidney cup. A small channel was made in the renal capsule and cortex with a 23-gauge needle; after cessation of bleeding, the microdialysis probe with 0.5-mm-tip diameter and a 20-kD transmembrane diffusion cutoff (Bioanalytical Systems) was inserted into the renal cortex to a depth of 1.5 mm. A second probe was inserted into the renal medulla (5 mm in depth). The cortical probe was then perfused at a rate of 2 µL/min with PBS containing Na2HPO4 50 mmol/L, NaH2PO4 50 mmol/L, NaCl 145 mmol/L, and OxyHb 0.003 mmol/L (pH 7.4). The medullary probe was perfused at the same perfusion rate with the same solution except that NaCl of a greater osmolality was used (NaCl 500 mmol/L). During a 1.5-hour equilibration period, the animal received an intravenous infusion of 2% bovine serum albumin in a 0.9% NaCl, at a rate of 1 mL/h per 100 g body wt, while microdialysis probes were perfused continuously at a rate of 2 µL/min. This equilibration time was to allow the tissue to recover from the insertion of the microdialysis probe.11 After the equilibration period, dialysate fluid was collected at 30-minute intervals for a 1-hour control measurement period. L-arginine was infused intravenously at a dose of 3 mg/kg per minute for 2 hours (n=6 rats), and the dialysate was collected after 30 minutes of L-arginine infusion. The dose of L-arginine was based on that used in a previous study, in which L-arginine markedly increased urine nitrite excretion and improved renal function.12 These dialysate samples were analyzed to record absorbance spectra of MetHb as described below. MetHb or NO concentration was calculated according to the equation c=A/
b, where c is MetHb or NO concentration, A is absorbance increase at 401 nm, is extinction coefficient of MetHb, and b is light path in centimeters. In a separate group of rats, L-NAME was infused intravenously at a dose of 10 µg/kg per minute for 2 hours (n=6 rats), and the dialysate was collected over 30-minute intervals after a 1-hour control period. This dose of L-NAME has been reported to decrease renal blood flow and increase arterial blood pressure in anesthetized rats.13 The collected dialysate samples were analyzed as described below.
In another series of experiments, we included SOD (200 U/mL) and catalase (600 U/mL) in the microdialysis perfusate. At these concentrations, they completely blocked the effects of xanthine/xanthine oxidase (a superoxide-producing system) on the spectrum of hemoglobin. These experiments were designed to exclude the possible effect of superoxide on the spectrum of MetHb. The dialysates were collected, and spectrophotometric analysis was performed as described below.
Effect of Renal Medullary Infusion of SNP on NO Concentration
To further confirm that MetHb in the microdialysate is derived from NO-mediated oxidation in renal tissue, the effect of renal medullary infusion of the NO donor SNP on measured MetHb or NO concentration was examined. These experiments were performed on 5 rats surgically prepared as described above. In addition, a small extruded polyethylene catheter with a 100-µm-diameter tip was implanted into the interstitium of the renal outer medulla as previously described5,6 to allow for administration of SNP directly into the renal medullary interstitium. After implantation, a 0.9% solution of NaCl as the vehicle control solution for drug delivery was continuously infused at a rate of 0.5 mL/h. Microdialysis probes were implanted into the renal medulla as described above. SOD and catalase were included in the microdialysis perfusate. After a 1.5-hour equilibration period and a 1-hour control collection period, SNP at a concentration of 1 mmol/L (0.5 mL/h) was infused into the renal medulla. After 1-hour infusion, the dialysate was collected for MetHb spectrum analysis.
Spectrophotometry Assay of NO-Induced MetHb Formation
The spectrophotometric hemoglobin-NO trapping technique is based on the rapid oxidation of ferrous OxyHb (Fe2+) to MetHb (Fe3+) by NO. The oxidation of ferrous hemoglobin is stoichiometric with NO and occurs in <100 ms. Because the oxidation of OxyHb to MetHb is characterized by changes in its absorbance that occurred between 401 and 411 nm, the difference in absorbance between 401 and 411 nm can be used to calculate MetHb or NO concentration according to the extinction coefficient of MetHb. Because the isobestic point for the conversion of OxyHb to MetHb occurs at 411 nm and should not change, the assay was simplified by measuring the increase in absorbance at 401 nm.14,15 This approach has been used widely for the quantitative determination of NO and kinetic studies of NO metabolism in in vitro biochemical experiments.16
Human Ao hemoglobin (ferrous) (Sigma) was used to trap NO. It was prepared in PBS, which contained Na2HPO4 50 mmol/L, NaH2PO4 50 mmol/L, and NaCl 145 mmol/L as a 25 mg/2 mL solution. This stock OxyHb solution (300 µmol/L) was quickly frozen at -80°C in small aliquots and used for 2 weeks. For the assay procedure, OxyHb was diluted to a working solution to provide the appropriate concentrations. A Du-640 Beckman spectrophotometer was used to determine changes in absorbance of MetHb and OxyHb at 401 and 411 nm and to record the spectra or differences in spectra of MetHb.
A calibration curve was constructed in vitro with the use of a saturated solution of NO, which was prepared as previously described.17 Briefly, 5 mL PBS was pipetted into a glass vial (6-mL-thick wall) with a rubber seal and deoxygenated by repeatedly vacuumizing and bubbling with argon for 1.5 hours; pure NO gas passed through a column of KOH pellets was injected as a fine stream into the vial. The concentration of this NO stock solution was 1.5 to 1.8 mmol/L. Different volumes of saturated NO solution were injected into the reaction mixtures with the use of gas-tight syringes to obtain various concentrations of NO. The molar extinction coefficient (), which is the calculated absorbance of a 1 mol/L solution of MetHb with a 1-cm light path, was obtained by quantitative oxidation of increasing amounts (0.75 to 12 µmol/L) of OxyHb by NO and measurement of absorbance increase at 401 nm.
To determine the applicability of SNP as an in vivo NO donor, we first examined in vitro the release of NO from SNP using the OxyHb trapping technique. SNP (1 mmol/L) was added to the reaction mixture containing 3 µmol/L OxyHb. NO release was evaluated in the presence or absence of SOD (200 U/mL) and catalase (600 U/mL), and difference spectra of MetHb were continuously recorded for 30 minutes. The addition of SOD and catalase blocked the possible effects of free radicals such as superoxide on the MetHb formation. We found that the concentrations of SOD and catalase used in these experiments completely inhibited the effect of superoxide in our preliminary experiments (data not shown).
Colorimetric Assay of Nitrite/Nitrate
Nitrite/nitrate concentration in the dialysate was measured with a colorimetric nitric oxide assay kit (Oxford). A microplate was used to perform enzyme reactions in vitro. For spectrophotometric assay of nitrite with Griess reagent, 80 mL MOPS (50 mmol/L)/EDTA (1 mmol/L) buffer and 5-µL dialysate samples were added to wells in duplicate. Nitrate reductase (0.01 U) and 10 µL NADH (2 mmol/L) were added to the reaction mixture, and the plate was shaken for 20 minutes at room temperature. Color reagents, sulfanilamide, and N-(1-Naphthyl) ethylenediamine dihydrochloride were added, and absorbance values at 540 nm were read in a microtiter plate reader (Bio-Rad model 3550). The concentration of nitrite/nitrate was estimated from a standard curve, which was constructed with the use of standard reagents included in the assay kit.
Statistical Analysis
Data are presented as mean±SE. The significance of differences within and between multiple groups was evaluated with the use of ANOVA for repeated measures followed by a Duncan’s multiple range test. Statistical differences between two groups were determined by Student’s t or paired t test. A value of P<.05 was considered statistically significant.
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Results |
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Characteristics of NO-Induced MetHb Formation
Addition of NO-saturated solution into the OxyHb reaction mixture produced a concentration-dependent increase in absorbance at 401 nm, indicating the formation of MetHb (Fig 1A). By oxidizing increasing amounts (0.75 to 12 µmol/L) of OxyHb with the use of NO-saturated solution, we calculated the molar extinction coefficient of MetHb as 112 000 M-1·cm-1, with a correlation coefficient of .998. There was a highly linear correlation between calculated NO concentration by MetHb formation and NO-saturated solution (r=.999) (Fig 1B).
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SNP released NO and oxidized OxyHb in a time-dependent manner. Maximal MetHb formation was observed at 30 minutes. SOD and catalase had no effect on the MetHb formation when added into the reaction mixture (Fig 2). SNP-released NO can be effectively dialyzed through the use of a microdialysis probe in vitro at a perfusion rate of 2 µL/min. A 97% relative recovery was observed (data not shown).
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Microdialysis Study In Vivo
The effects of intravenous infusion of L-NAME on NO concentration in the interstitial fluid of the renal cortex and medulla are presented in Fig 3. The basal concentration of NO was significantly higher in the renal medulla, averaging 57.1±5.6 nmol/L compared with 31.2±5.7 nmol/L in the renal cortex (P<.05). Intravenous infusion of L-NAME decreased NO by 33% in the renal cortex and by 46.5% in the renal medulla.
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In contrast to the effect of L-NAME, intravenous infusion of L-arginine produced a twofold to threefold increase in cortical and medullary NO (Fig 4). Addition of SOD and catalase to the microdialysis perfusate did not alter baseline NO levels or the effect of L-NAME and L-arginine on cortical and medullary NO concentration (Figs 3 and 4
).
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Nitrite/nitrate concentration was 2.7±0.6 µmol/L in the renal medulla and 2.1±0.2 µmol/L in the renal cortex. Intravenous infusion of L-NAME reduced renal interstitial nitrite/nitrate concentration by 18% in the renal cortex and 23% in the renal medulla, and intravenous infusion of L-arginine increased cortical and medullary nitrite/nitrate concentrations by 65% and 39%, respectively (Fig 5).
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Effect of Renal Medullary Infusion of SNP on NO Concentration
Changes in NO concentrations in the renal medulla during medullary infusion of SNP are presented in Fig 6. When SNP (1 mmol/L) was infused into the renal medullary interstitium, the concentration of dialyzed NO from the renal medulla was significantly increased. Cortical NO concentrations were not measured in the study.
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Discussion |
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The present study provides the first direct evidence that NO concentration in the renal medulla is higher than in the renal cortex. The responsiveness of the technique was demonstrated by L-arginine and SNP stimulation and L-NAME inhibition of NO release. These studies demonstrated that NO trapping through the use of OxyHb in combination with in vivo microdialysis is a practical and useful method for the detection of tissue NO in the renal cortex and medulla.
There have been a number of approaches used in efforts to indirectly provide indexes of tissue NO production and release. Assay of guanylyl cyclase activity and measurement of citrulline conversion rate have been used to determine NOS activity, but NO levels cannot be measured directly by these methods.7 Detection of luminescence of products of ozone with NO has been used to estimate NO levels. However, since this technique measures NO in the gas phase, the stripping of NO from a liquid biological sample for release into the gas phase is a complicated process, in which proteinaceous material foams dramatically during stripping. This results in coating of the photomultiplier tube for luminescence measurement and diminishes its sensitivity.18,19
Amperometric or voltametric microprobes have been developed recently to determine NO from intact tissues or single cells.20,21 A glass Clark-like microelectrode with a platinum cathode shows current alteration at 0.9 V, which is specific for NO,20 but these microprobes exhibit a large variation in sensitivity. A second, more sensitive microprobe is based on the observation that metalloporphyrins catalyze the oxidation of NO and consequently generate electrical current. A carbon fiber is coated with a thin polymeric porphyrin layer, and this electrode can be used to measure NO as the electrical current produced at 0.63 V. Although an additional coat of the carbon fiber with a negatively charged material, perfluorinated ionomer (Nafion) makes the microprobe impermeable to anions such as NO2-, catecholamines can still react with carbon fiber and produce the current. These probes are also quite fragile and problematic for measurements with deep tissue regions such as the renal medulla. Therefore, variable sensitivity, limited specificity, as well as high fragility of microprobes for NO plague the usefulness of these electrodes in in vivo systems.21,22
The measurements of nitrite/nitrate as NO end products have been used to determine NO levels in different samples and preparations,23 but this assay is only adequate as a qualitative or semiquantitative measure of NOS-related activity.24 Urinary nitrite/nitrate has been used to represent NO levels in the kidney,25,26 but such measurements cannot distinguish regional differences between cortical and medullary NO production. In addition, urinary nitrite/nitrate is produced not only in the kidney, and the renal reabsorption and excretion of nitrite/nitrate is complicated, making measurement of nitrite/nitrate very limiting in defining the role of NO in the regulation of renal function.
NO trapping technique using OxyHb has been used to study NO release from pharmacological NO donors, NOS activity, enzyme kinetics, and NO production in isolated perfused organs and cultured or fresh cells.16 Recent studies indicated that a microdialysis probe using a hemoglobin-trapping technique possesses adequate sensitivity to determine the basal levels of NO in the brain and changes in NO level induced by a neurotoxin, kainic acid.27 In the present study, we used in vivo microdialysis in combination with a hemoglobin-trapping technique to examine NO levels in the renal cortex and medulla and the effect of L-arginine and its analogue, L-NAME, on NO levels in both regions. We found that NO concentrations in the renal cortex and medulla were 31.2 and 57.1 nmol/L, respectively, in anesthetized rats. A higher NO level in the renal medulla may be associated with greater expression of NOS in this region. Studies in our laboratory and others have demonstrated that the expression of NOS including cNOS, nNOS, and iNOS in the renal medulla was much greater than in the renal cortex.10 Intravenous infusion of L-arginine as a substrate of NO formation produced a marked increase in cortical and medullary NO, and infusion of L-NAME reduced NO levels in both regions. Using the nitrite/nitrate colorimetric assay, we found that nitrite/nitrate concentration in the dialysate from the renal medulla and cortex was altered in the same direction as NO concentration when L-arginine and L-NAME were infused intravenously. However, the magnitude of alterations in nitrite/nitrate was smaller than hemoglobin-trapped NO. These results indicate that the microdialysis and hemoglobin-trapping technique can be used in the kidney for the in vivo detection of regional concentration of NO.
Because free radicals such as superoxide can be formed in the kidney and NOS itself can also catalyze the production of the oxidant superoxide,28 we were concerned whether in vivo superoxide anions could be dialyzed and directly influence the formation of MetHb, thereby producing an artifactual change in measured NO concentrations. To examine this issue, we included a high concentration of SOD and catalase in the dialysis perfusate to effectively scavenge superoxide and H2O2. The values of NO in the renal cortex and medulla were compared with those obtained in the absence of these scavengers of free radicals. We found that MetHb formation (characterized by increase in absorbance at 401 nm) in both medullary and cortical dialysates was not altered by removal of superoxide anions by SOD and catalase, suggesting that superoxide anions and H2O2 did not influence the MetHb formation in the dialysate from the renal medulla and cortex. The finding that local medullary administration of the NO donor SNP markedly increased MetHb concentration in the dialysate in the presence of SOD and catalase further supports the view that MetHb in the dialysate is due to the oxidation of OxyHb by NO, not by superoxide anions. It is important to note that peroxynitrite, a product of NO and superoxide, has been reported to induce spectral changes of OxyHb identical with those elicited by NO.29 Therefore, we cannot exclude the possibility that MetHb in the dialysate may be in part derived from peroxynitrite formed in the tissue. However, since peroxynitrite formation in the tissue requires NO, MetHb in the dialysate derived even from tissue peroxynitrite also reflects changes in NO levels.
In summary, the in vivo microdialysis and hemoglobin-trapping technique is useful for determining tissue concentration of NO in the kidney. NO concentrations in the renal medulla are much higher than in the renal cortex. A high level of medullary NO may play an important role in the control of vascular tone and tubular function in the renal medulla.
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Acknowledgments |
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This study was supported by grant HL-29587 from the National Institutes of Health, Bethesda, Md. The authors thank Drs Balaraman Kalyanaraman and Neil Hogg for their helpful discussion and for helping to prepare the NO-saturated solution.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Baylis C, Harton P, Ebgels K. Endothelial derived relaxing factor controls renal hemodynamics in the normal rat kidney. J Am Soc Nephrol. 1990; 1 : 875 –881.[Abstract]
- King AJ, Brenner BM. Endothelium-derived vasoactive factors and the renal vasculature. Am J Physiol. 1991; 260 : F653 –F662.
- Romero JC, Lahera V, Salom MG, Biondi ML. Role of endothelium-dependent relaxing factor nitric oxide on renal function. J Am Soc Nephrol. 1992; 2 : 1371 –1387.[Abstract]
- Navar GL, Inscho EW, Majid SA, Imig JD, Harrison-Bernard L, Mitchell KD. Paracrine regulation of the renal microcirculation.
Physiol Rev. 1996;
76
: 425
–536.
[Abstract/Free Full Text] - Mattson DL, Lu S, Nakanishi K, Papanek PE, Cowley AW Jr. Effect of chronic renal medullary nitric oxide inhibition on blood pressure. Am J Physiol. 1994; 266 : H1918 –H1926.[Medline] [Order article via Infotrieve]
- Nakanishi K, Mattson DL, Cowley AW Jr. Role of renal medullary blood flow in the development of L-NAME hypertension in rats. Am J Physiol. 1995; 268 : R317 –R323.
- Biondi ML, Dousa TP, Vanhoutte PM, Romero JC. Evidence for the existence of endothelium-derived relaxing factor in the renal medulla. Am J Hypertens. 1990; 3 : 876 –878.[Medline] [Order article via Infotrieve]
- Biondi ML, Romero JC. Nitric oxide mediated reactions stimulate cyclic GMP in the dog kidney. J Vasc Med Biol. 1990; 2 : 294 –298.
- Biondi ML, Bolterman RJ, Romero JC. Zonal changes of guanidine 3'5' cyclic monophosphate related to endothelium-derived relaxing factor in dog renal medulla. Renal Physiol Biochem. 1992; 15 : 1 –7.[Medline] [Order article via Infotrieve]
- Mattson DL, Higgins DJ. Influence of dietary sodium intake on renal medullary nitric oxide synthase.
Hypertension. 1996;
27
(part 2): 688
–692.
[Abstract/Free Full Text] - Baranowski RL, Westenfelder C. Estimation of renal interstitial adenosine and purine metabolites by microdialysis. Am J Physiol. 1994; 267 : F174 –F182.[Medline] [Order article via Infotrieve]
- Ikenaga H, Suzuki H, Ishi N, Itoh H, Saruta T. Role of NO on pressure-natriuresis in Wistar-Kyoto and spontaneously hypertensive rats. Kidney Int. 1993; 43 : 205 –211.[Medline] [Order article via Infotrieve]
- Lehera V, Salom MG, Mirauda-Guardiola F, Moncada S, Romero JC. Effects of NG nitro-L-arginine methyl ester on renal function and blood pressure. Am J Physiol. 1991; 261 : F1033 –F1037.[Medline] [Order article via Infotrieve]
- Feelisch M, Noack EA. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987; 139 : 19 –30.[Medline] [Order article via Infotrieve]
- Hevel JM, Marletta MA. Nitric-oxide synthase assays. Methods Enzymol. 1994; 233 : 251 –258.
- Feelisch M, Kubitzek D, Werringloer J. The oxyhemoglobin assay. In: Feelisch M, Stamler JS, eds. Methods in Nitric Oxide Research. New York, NY: John Wiley & Sons Ltd; 1996: 455 –478.
- Ravichandran LV, Johns RA, Rengasamy A. Direct and reversible inhibition of endothelial nitric oxide synthase by nitric oxide. Am J Physiol. 1995; 268 : H2216 –H2223.[Medline] [Order article via Infotrieve]
- Aoki T. Continuous flow determination of nitrite with membrane separation/chemiluminescence detection. Biomed Chromatogr. 1990; 4 : 128 –130.[Medline] [Order article via Infotrieve]
- Archer S. Measurement of nitric oxide in biological models. FASEB J. 1993; 7 : 349 –360.[Abstract]
- Shibuki K, Okada D. Endogenous nitric oxide release required for longterm synaptic depression in the cerebellum. Nature. 1991; 349 : 326 –328.[Medline] [Order article via Infotrieve]
- Malinski T, Taha Z. Nitric oxide release from a single cell measured in situ by a porphyrine-based microsensor. Nature. 1992; 358 : 676 –678.[Medline] [Order article via Infotrieve]
- Balcioglu A, Maher TJ. The measurement of nitric oxide release induced by kainic acid using a novel hemoglobin-trapping technique with microdialysis. Ann N Y Acad Sci. 1994; 738 : 282 –287.[Medline] [Order article via Infotrieve]
- Schmidt HHHW, Kelm M. Determination of nitrite and nitrate by the Griess reaction. In: Feelisch M, Stamler JS, eds. Methods in Nitric Oxide Research. New York, NY: John Wiley & Sons Ltd; 1996: 491 –497.
- Feelisch M, Stamler JS. Measurement of NO-related activities: which assay for which purpose? In: Feelisch M, Stamler JS, eds. Methods in Nitric Oxide Research. New York, NY: John Wiley & Sons Ltd; 1996: 303 –307.
- Schultz PJ, Tolins JP. Adaptation to increased dietary salt intake in the rat: role of endogenous nitric oxide. J Clin Invest. 1993; 91 : 642 –650.[Medline] [Order article via Infotrieve]
- Tolins JP, Shultz PJ. Endogenous nitric oxide synthesis determines sensitivity to the pressor effect of salt. Kidney Int. 1994; 46 : 230 –236.[Medline] [Order article via Infotrieve]
- Balcioglu A, Maher TJ. Determination of kainic acid-induced release of nitric oxide using a novel hemoglobin trapping technique with microdialysis. J Neurochem. 1993; 61 : 2311 –2313.[Medline] [Order article via Infotrieve]
- Culcasi M, Cafon-Cazal M, Pietri S, Bockaert J. Glutamate receptors induce a burst of superoxide via activation of nitric oxide synthase in arginine depleted neurons.
J Biol Chem. 1994;
269
: 12589
–12593.
[Abstract/Free Full Text] - Schmidt K, Klatt P, Mayer B. Reaction of peroxynitrite with oxy-haemoglobin: interference with photometrical determination of nitric oxide. Biochem J. 1994; 301 : 645 –647.[Medline] [Order article via Infotrieve]
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H. Matsuda, K. Hayashi, S. Wakino, E. Kubota, M. Honda, H. Tokuyama, I. Takamatsu, S. Tatematsu, and T. Saruta Role of Endothelium-Derived Hyperpolarizing Factor in ACE Inhibitor-Induced Renal Vasodilation in Vivo Hypertension, March 1, 2004; 43(3): 603 - 609. [Abstract] [Full Text] [PDF]
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T. Zewde, F. Wu, and D. L. Mattson Influence of dietary NaCl on L-arginine transport in the renal medulla Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R89 - R93. [Abstract] [Full Text]
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L. A. Fortepiani, M. C. O. Ruiz, F. Passardi, M. D. Bentley, J. Garcia-Estan, E. L. Ritman, and J. C. Romero Effect of losartan on renal microvasculature during chronic inhibition of nitric oxide visualized by micro-CT Am J Physiol Renal Physiol, November 1, 2003; 285(5): F852 - F860. [Abstract] [Full Text] [PDF]
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Y.-F. Chen, A. W. Cowley Jr., and A.-P. Zou Increased H2O2 counteracts the vasodilator and natriuretic effects of superoxide dismutation by tempol in renal medulla Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R827 - R833. [Abstract] [Full Text] [PDF]
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F. Rodriguez, R. Kemp, M. Balazy, and A. Nasjletti Effects of Exogenous Heme on Renal Function: Role of Heme Oxygenase and Cyclooxygenase Hypertension, October 1, 2003; 42(4): 680 - 684. [Abstract] [Full Text] [PDF]
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A. Makino, M. M. Skelton, A.-P. Zou, and A. W. Cowley Jr Increased Renal Medullary H2O2 Leads to Hypertension Hypertension, July 1, 2003; 42(1): 25 - 30. [Abstract] [Full Text] [PDF]
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A. W. Cowley Jr., T. Mori, D. Mattson, and A.-P. Zou Role of renal NO production in the regulation of medullary blood flow Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1355 - R1369. [Abstract] [Full Text] [PDF]
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J. F. Reckelhoff and J. C. Romero Role of oxidative stress in angiotensin-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R893 - R912. [Abstract] [Full Text] [PDF]
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A. O. Oyekan Contributions of Nitric Oxide and Prostanoids and Their Signaling Pathways to the Renal Medullary Vasodilator Effect of U46619 (9-11-Dideoxy-11{alpha},9a-Epoxymethano-Prostaglandin F2a) in the Rat J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 507 - 512. [Abstract] [Full Text] [PDF]
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T. L. Pallone, Z. Zhang, and K. Rhinehart Physiology of the renal medullary microcirculation Am J Physiol Renal Physiol, February 1, 2003; 284(2): F253 - F266. [Abstract] [Full Text] [PDF]
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N. Tian, A. W. Gannon, R. A. Khalil, and R. D. Manning Jr. Mechanisms of salt-sensitive hypertension: role of renal medullary inducible nitric oxide synthase Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R372 - R379. [Abstract] [Full Text] [PDF]
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N. Li, F.-X. Yi, E. Rute, D. X. Zhang, G. R. Slocum, and A.-P. Zou Effects of homocysteine on intracellular nitric oxide and superoxide levels in the renal arterial endothelium Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1237 - H1243. [Abstract] [Full Text] [PDF]
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M. Szentivanyi Jr., A.-P. Zou, D. L. Mattson, P. Soares, C. Moreno, R. J. Roman, and A. W. Cowley Jr. Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R266 - R272. [Abstract] [Full Text] [PDF]
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A. Makino, M. M. Skelton, A.-P. Zou, R. J. Roman, and A. W. Cowley Jr Increased Renal Medullary Oxidative Stress Produces Hypertension Hypertension, February 1, 2002; 39(2): 667 - 672. [Abstract] [Full Text] [PDF]
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