doi: 10.1161/hy0202.104137
(Hypertension. 2002;39:293.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Nitric Oxide Blockade Enhances Renal Responses to Superoxide Dismutase Inhibition in Dogs
From the Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, La 70112. Present address for Akira Nishiyama is Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Correspondence to Dr Dewan S.A. Majid, Department of Physiology, SL 39, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112. E-mail majid{at}tulane.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
To examine the potential role of superoxide anion (O2-) and its interaction with NO in the regulation of renal hemodynamics and excretory function, we have evaluated the renal responses to enhancement in O2- activity before and during NO synthase inhibition in anesthetized dogs (n=6). Intraarterial infusion of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DETC; 0.1 and 0.5 mg/kg per min) was made to enhance O2- activity in the kidney. Cortical (CBF), medullary (MBF), and total renal blood flow (RBF) responses were assessed using laser-Doppler needle flow probes and an electromagnetic flow probe. DETC caused dose-dependent changes in renal parameters, which were recovered within 30 minutes after the termination of DETC infusion. The high-dose infusion of DETC for 25 minutes resulted in an increase of 29±10% in renal vascular resistance (control, 35.4±4.4 mm Hg/mL per min per g) and decreases of 21±5% in RBF (control, 3.5±0.5 mL/min per g), 20±5% in CBF, 21±7% in MBF, 62±11% in urine flow (control, 10.5±2.2 µL/min per g), and 47±11% in sodium excretion (control, 2.1±0.2 µmol/min per g), without a significant change (-10±6%) in glomerular filtration rate (control, 0.74±0.09 mL/min per g). During NO synthase inhibition with intraarterial administration of nitro-L-arginine (50 µg/kg per min), the same dose of DETC showed a greater increase in renal vascular resistance (73±15%) and reductions in RBF (39±4%), CBF (32±5%), MBF (34±6%), urine flow (78±5%), and sodium excretion (67±10%), with a marked reduction in glomerular filtration rate (59±7%). These data indicate that O2- exerts renal vasoconstriction as well as antidiuretic and antinatriuretic effects. These responses are enhanced during NO synthase blockade, suggesting that NO serves a renoprotective effect against these action of O2-.
Key Words: renal hemodynamics • renal regional blood flow • sodium excretion • diethyldithiocarbamate
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Partial reduction of molecular oxygen in living tissues can generate reactive oxygen species (ROS), including hydrogen peroxide and the free radicals superoxide (O2-) and hydroxyl ions.1,2 Over the past decade, there has been accumulating evidence for a role of ROS in the pathogenesis of a variety of renal diseases that involve vascular, glomerular, tubular, and renal interstitial damage.2–5 Recent studies have indicated a strong association of hypertension with increased production of O2-, which is a relatively abundant ROS in the living tissue.4,6–8 Both short-term and long-term inhibition of endogenous O2- formation have been shown to reduce blood pressure in spontaneously hypertensive rats.9,10
Although the role of O2- in hypertension has been suggested in many studies, the exact mechanism involved in this pathophysiology is not yet clearly established.4,11 It is known that O2- reacts with NO to form peroxynitrite, which could oxidize arachidonic acid and release a potent vasoconstrictor substance, 8-isoprostane.11,12 The reaction between NO and O2- to form peroxynitrite has a 3-fold faster rate constant than that of the reaction of superoxide dismutase (SOD) enzyme with O2- to form hydrogen peroxide.13 It has been suggested that the interaction of NO with O2- has greatly influence in determining the extent of vascular reactivity to NO in the biological tissue.14 Under normal conditions, O2- is a minor but constant product of the cellular metabolism.1,2 As the presence of O2- can diminish the half-life of NO, the potential role of O2-/NO interaction in the regulation of many biological events has been a major focus of many recent studies.11,14 It has been suggested that NO plays an important cytoprotective role against the injurious effects of O2- by acting as an antioxidative agent.14,15 Although experimental evidence has been amassed to indicate a key mediatory role for O2- in the pathophysiological processes of various renal disease entities, its possible role in the physiological regulation of renal function is not yet clear in the literature. Recent studies in rats by Zou et al16 indicated that O2- production in the renal medulla exerts vasoconstrictor as well as antidiuretic and antinatriuretic actions in the kidney. However, the role of O2- in regulating whole kidney hemodynamics, particularly in the control of glomerular filtration rate (GFR), has not been addressed in any previous study. Moreover, an interactive role of O2- and NO in the regulation of whole kidney blood flow and excretory function is not yet clearly defined.
The present investigation was designed to examine the hypothesis that NO activity reciprocally regulates intrarenal O2- level, which has direct influence on renal hemodynamics and tubular function, leading to alterations in net sodium reabsorption rate. The objective of this study is to evaluate the effects of enhanced O2- level and its interaction with NO in the control renal hemodynamics and excretory function. In these experiments, renal responses to SOD inhibition with diethyldithiocarbamate (DETC) were assessed before and during NO inhibition with nitro-L-arginine (NLA)16–18 in anesthetized dogs.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The experiments were performed in accordance with the guidelines and practices established by the Tulane University Animal Care and Use Committee.
Experiments were performed in 6 mongrel dogs (17 to 22 kg body wt) of either gender. To achieve a sodium replete state, the dogs were given supplemental amounts of sodium chloride (1.5 g/kg body wt per day for 3 days) added to the normal laboratory diet. The animals were anesthetized with pentobarbital sodium (30 mg/kg IV) and given additional doses as required. The surgical preparation of the animals and basic experimental techniques are identical to those previously described.19,20
The experimental protocol was started with urine collections for 2 consecutive 10-minute control periods, with an arterial blood sample (2 mL) taken at the midpoint of each collection period. This was followed by first a low dose (0.1 mg/kg per min) and then a high dose (0.5 mg/kg per min) of intraarterial infusions of DETC. During each dose infusion, an initial 5-minute stabilization period was allowed before two 10-minute collections of urine were made. After the termination of DETC infusion, 10 minutes was allowed for stabilization before the collection of 2 more 10-minute urine samples to assess the recovery of the renal parameters. An intraarterial infusion of NLA was then started at a dose of 50 µg/kg per min and continued for the duration of the experiment. After 10 minutes of stabilization, two more 10-minute urine samples were collected during NLA infusion alone. Then the infusions of low and high doses of DETC were repeated in the presence of NLA.
At the end of each experiment, the electromagnetic flow probe was calibrated in situ by timed collections of blood into a graduated cylinder from a catheter placed in the renal artery. The kidney was then removed, stripped of all surrounding tissue, blotted dry, and weighed so that the calculated parameters could be expressed per gram of kidney weight. Flame photometry (Instrumentation Laboratory) was used to determine the sodium concentrations in plasma and urine. Inulin concentrations in the samples were determined by the anthrone colorimetric technique (Gilford Instruments).
Values are reported as mean±SE. Statistical comparisons of differences in the responses were conducted with the use of ANOVA, followed by Newman-Keuls test. Differences in the mean values were deemed significant at P<0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Responses to Infusion of DETC on Renal Hemodynamics and Excretory Function Before NLA Administration
The table summarizes the results in absolute mean values obtained in 6 dogs. The values are the average of the values obtained in two 10-minute collection periods. The percent changes in the responses are illustrated in Figures 1 through 4. Intrarenal infusions of both low and high doses of DETC did not cause any significant change in systemic arterial pressure (Table). Renal vascular resistance (RVR) did not change during low-dose infusion of DETC but increased significantly during high-dose infusion (Table and Figure 1). Low dose of DETC failed to cause any significant change in total RBF (-2±2%), cortical blood flow (CBF, -3±3%), and medullary blood flow (MBF, 0.3±5%); however, high dose caused reductions of 21±5% in RBF, 20±5% in CBF, and 21±7% in MBF (Figures 1 and 2, Table). GFR did not alter significantly during infusion of these DETC doses (Figure 3, Table). There were dose-dependent changes in urine flow and sodium excretion (UNaV) during DETC infusion. Urine flow decreased to 24±12% and 62±11% during low- and high-dose DETC infusions, respectively. Similarly, UNaV decreased to 38±14% and 47±10% during infusions of both low and high doses, respectively. Fractional excretion of sodium (FENa) also decreased dose-dependently. These changes in renal hemodynamics and excretory function in response to DETC were seen reversed within 30 minutes of cessation of the DETC infusion. The values in the renal parameters during the postcontrol period are not significantly different from values obtained during control periods. (Table).
|
|
|
|
|
Responses to DETC on Renal Hemodynamics and Excretory Function During NLA Administration
During inhibition of NO synthase by intraarterial infusion of NLA, there were increases in arterial pressure and RVR and decreases in RBF, CBF, MBF, urine flow, UNaV, and FENa, without changes in the GFR, as reported previously.17,18 The summarized results have been given in the Table. In the presence of NLA, there was enhancement of the renal responses to DETC. The Table summarizes the responses in absolute mean values, and Figures 1 through 4 illustrate the responses in percent changes. Although low-dose DETC before NLA infusion did not cause any effects on renal hemodynamics, it caused increases in arterial pressure and RVR and decreases in RBF, CBF, and MBF (Figures 1 and 2, Table). Both low- and high-dose infusions of DETC caused an increase in RVR (27±8% and 73±15%) and decreases in RBF (19±4% and 39±4%), CBF (20±6% and 32±5%), and MBF (19±7% and 34±6%), respectively, during NLA infusion. There were dose-dependent marked reductions in GFR (31±9% and 59±7%) during infusion of the doses of DETC in NO synthase–blocked dogs (Figure 3). Greater reductions in urine flow (57±6% and 78±5%) and UNaV (53±9% and 67±10%) were also observed in response to DETC doses infusion in the presence of NLA (Figure 4).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The present investigation demonstrates that intraarterial administration of a SOD inhibitor, DETC, in anesthetized dogs would enhance O2- activity in the kidney and result in an increase in RVR and reductions in the basal levels of RBF, urine flow, and UNaV. These changes to DETC were greatly enhanced during NLA infusion, indicating that NO interacts with O2- to prevent its renal vasoconstriction as well as antidiuretic and antinatriuretic effects. DETC, a copper cheating agent, has been used in many previous studies to examine the role of enhanced O2- activity in the biological tissues.15,16,21–23 It was shown that the high dose of DETC used in the present study was effective in producing 80% inhibition of SOD activity.24 In an in vitro study, Pagano et al25 demonstrated the O2- levels (measured by leuigenin chemiluminescence assay) in isolated blood vessels increased nearly 10-fold during application of 10 mmol/L DETC. In a separate in vitro study using isolated rat aorta, we also observed that application of DETC (10 mmol/L) caused an increased level of O2-, which was reversed by the addition of tempol (3 mmol/L) (Nishiyama A, Shokoji T, Abe Y, unpublished observation, 2001).
In the present study, it is noted that low-dose infusion of DETC before NLA infusion did not cause appreciable changes in RBF or GFR but was able to cause substantial reductions in urine flow and UNaV. These results indicated that O2- activity in the kidney may directly influence the tubular reabsorptive function without concomitant changes in renal hemodynamics. During NO inhibition, there was a marked reduction in GFR in response to DETC administration, which was not observed before NLA infusion (Figure 3). These findings strongly suggest that NO provides a renoprotective function against the effects of O2- to maintain the basal filtration rate in the glomerulus.
Our findings in anesthetized dogs are in agreement with those of a recent study in rats by Zou et al,16 who demonstrated that intramedullary administration of DETC at a rate of 0.5 mg/kg per min also caused vasoconstrictor and antinatriuretic effects. They also examined the biomedical pathways responsible for O2- production in the kidney and observed that the outer medullary and cortical regions contain all the major O2--producing enzymes, such as NADH/NADPH oxidase and mitochondrial respiratory chain enzyme. Our findings that DETC administration resulted in both cortical and medullary vasoconstriction suggest that enhancement of O2- activity induced by DETC occurred in both the cortical and medullary regions in the kidney. In the present study, simultaneous evaluation of the responses to enhancement of O2- activity on total and regional blood flows, GFR, and renal excretory function has been made more comprehensively in the presence and absence of NO synthase blockade in the kidney.
It is generally believed that O2--induced vasoconstriction is mainly caused by abolition of NO-mediated vasodilation, as both these oxygen radicals interact with each other.14,15 However, we have observed that renal vasoconstrictor responses to DETC infusion were greatly enhanced in the absence of NO generation. This finding clearly indicates that O2- can exert renal vasoconstrictor effects independent of NO mechanism. The exact mechanism by which O2- can induce vasoconstriction is not yet clear. However, it was reported that an excessive intracellular calcium accumulation could be observed in myocardium because of oxidant stress during ischemic condition in heart.26–28 Thus, it is possible that an increase in intracellular calcium level induced by O2- generation in vascular smooth muscles can cause such direct vasoconstrictor effect. Our results also indicate that O2- may have an influence on renal tubular reabsorption independent of NO, as the effects of DETC on urine flow and UNaV were seen to be markedly enhanced during NO synthase inhibition. Thus, it is clear that NO and O2- exert a reciprocal effect on renal tubular reabsorptive function, as NO generally induces diuretic and natriuretic responses in the kidney.18,20 The mechanism involved in the tubular effect of O2- is not yet clear. Further studies are needed to characterize the exact nature of O2- involvement on the vascular and tubular function in the kidney.
The cellular levels of NO and O2- production and their interactions are believed to have a major impact on the expression of signaling mechanisms that control vascular reactivity.15,21 It is conceivable that the biological stability of NO and its signaling mechanisms are more likely to be controlled by the levels of O2- generated within the cellular tissue. Omar et al21 have demonstrated that the relaxation of endothelium-removed bovine coronary arteries to a NO donor is attenuated by pretreatment with an inhibitor of SOD, and this effect is prevented by a scavenger of intracellular O2-. The findings in that study21 show how the scavenging of endogenous O2- by SOD protects NO from being inactivated by this oxidant. Thus, it is conceivable that if there is an imbalance in the production of NO and O2-, the major signaling effect observed is likely to be an alterations in NO-elicited vascular relaxing and other effects.14 Apart from its vascular relaxing effects, NO also regulates other cellular mechanisms such as prostaglandin production by vascular endothelium,21,29 mitochondrial oxygen metabolism,14 cellular membrane ionic channels, and their dependent signaling mechanisms15 and, particularly in the kidney, regulates the ionic channel activity in epithelial cells involved in tubular reabsorptive mechanism.30 Thus, processes originating from the interaction of O2- with NO have the potential to influence the endothelial, epithelial, and other cellular functions in the organs.
In conclusion, the results of the present investigation indicate that O2- exerts renal vasoconstriction and tubular effects, leading to salt and water retention. These data are consistent with the hypothesis that NO serves an important protective role against the actions of O2- in the kidney.
|
Acknowledgments |
|---|
This study was supported by grants HL-51306 and HL-66432 from the National Heart, Lung and Blood Institute, National Institutes of Health (D.S.A.M.), and an award from the American Heart Association, Southeast Affiliate (A.N.). We are grateful to David E. Moliere for technical assistance and Debbie Olavarrieta for excellent secretarial support in preparing the manuscript.
Received July 30, 2001; first decision September 4, 2001; accepted December 11, 2001.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Baud L, Ardaillou R. Reactive oxygen species: production and role in the kidney. Am J Physiol. 1986; 251: F765–F776.[Medline] [Order article via Infotrieve]
2. Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney Int. 1994; 45: 1–9.[Medline] [Order article via Infotrieve]
3. Heitzer T, Wenzel U, Hink U, Krollner D, Skatchkov M, Stahl RAK, Macharzina R, Bräsen JH, Meinertz T, Münzel T, Increased NAD(P)H oxidase-mediated superoxide production in renovascular hypertension: evidence for an involvement of protein kinase C. Kidney Int. 1999; 55: 252–260.[CrossRef][Medline] [Order article via Infotrieve]
4. Kitiyakara C, Wilcox CS. Antioxidants for hypertension. Curr Opin Nephrol Hypertens. 1998; 7: 531–538.[Medline] [Order article via Infotrieve]
5. McIntyre M, Bohr DF, Dominiczak AF. Endothelial function in hypertension: the role of superoxide anion. Hypertension. 1999; 34: 539–545.
6. Laursen JB, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG. Role of superoxide in angiotensin II–induced but not catecholamine-induced hypertension. Hypertension. 1997; 95: 588–593.
7. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II–mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation: contribution to alterations of vasomotor tone. J Clin Invest. 1996; 97: 1916–1923.[Medline] [Order article via Infotrieve]
8. Wang HD, Hope S, Du Y, Quinn MT, Cayatte A, Pagano PJ, Cohen Ra. Paracrine role of adventitial superoxide anion in mediating spontaneous tone of the isolated rat aorta in angiotensin II–induced hypertension. Hypertension. 1999; 33: 1225–1232.
9. Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension. 1998; 32: 59–64.
10. Schnackenberg CG, Wilcox CS. Two-week administration of tempol attenuates both hypertension and renal excretion of I-iso prostaglandin F2
. Hypertension. 1999; 33(pt 2): 424–428.
11. Haas JA, Krier JD, Bolterman RJ, Juncos LA, Romero JC. Low-dose angiotensin II increases free isoprostane levels in plasma. Hypertension. 1999; 34(pt 2): 983–986.
12. Beckman JS, Crow JP. Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans. 1993; 21: 330–334.[Medline] [Order article via Infotrieve]
13. Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun. 1993; 18: 195–199.[Medline] [Order article via Infotrieve]
14. Wolin MS, Gupte SA, Iesaki T, Mohazzab-H KM. Oxidants and vascular nitric oxide signaling. In: Kadowitz PJ, McNamara DB, eds. Nitric Oxide and the Regulation of the Peripheral Circulation. Boston: Birkhäuser; 2000: 33–48.
15. Mugge A, Elwell JH, Peterson TE, Harrison DG. Release of intact endothelium-derived relaxing factor depends on endothelial superoxide dismutase activity. Am J Physiol. 1991; 260: C219–C225.[Medline] [Order article via Infotrieve]
16. Zou A-P, Li N, Cowley AW Jr. Production and actions of superoxide in the renal medulla. Hypertension. 2001; 37: 547–553.
17. Majid DSA, Navar LG. Suppression of blood flow autoregulation plateau during nitric oxide blockade in canine kidney. Am J Physiol. 1992; 262: F40–F46.[Medline] [Order article via Infotrieve]
18. Majid DSA, Williams A, Kadowitz PJ, Navar LG. Renal responses to intra-arterial administration of nitric oxide donor in dogs. Hypertension. 1993; 22: 535–541.
19. Majid DSA, Godfrey M, Navar LG. Pressure natriuresis and renal medullary blood flow in dogs. Hypertension. 1997; 29: 1051–1057.
20. Majid DSA, Said KE, Omoro SA, Navar LG. Nitric oxide dependency of arterial pressure–induced changes in renal interstitial hydrostatic pressure in dogs. Circ Res. 2001; 88: 347–351.
21. Omar HA, Cherry PD, Mortelliti MP, Burke-Wolin T, Wolin MS. Inhibition of coronary artery superoxide dismutase attenuates endothelium-dependent and -independent nitrovasodilator relaxation. Circ Res. 1991; 69: 601–608.
22. De Man JG, De Winter BY, Boeckxstaens GE, Herman AG, Pelckmans PA. Effect of thiol modulators and Cu/Zn superoxide dismutase inhibition on nitrergic relaxations in the rat gastric funders. Br J Pharmacol. 1996; 119: 1022–1028.[Medline] [Order article via Infotrieve]
23. Pritsos CA, Keyes SR, Sartorelli AC. Effect of the superoxide dismutase inhibitor, diethyldithiocarbamate, on the cytotoxicity of mitomycin antibiotics. Cancer Biochem Biophys. 1989; 10: 289–298.[Medline] [Order article via Infotrieve]
24. Rothstein JD, Bristol LA, Hosler B, Brown RH, Kuncl RW. Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc Natl Acad Sci U S A. 1994; 91: 4155–4159.
25. Pagano PJ, Griswold MC, Najibi S, Marklund SL, Cohen Ra. Resistance of endothelium-dependent relaxation to elevation of O2- levels in rabbit carotid artery. Am J Physiol. 1999; 277: H2109–H2114.[Medline] [Order article via Infotrieve]
26. Tani M. Mechanisms of Ca2+ overload in reperfused ischemic myocardium. Ann Rev Physiol. 1990; 52: 543–549.[Medline] [Order article via Infotrieve]
27. Wu QY, Fehr JJ. Effect of ischemia-reperfusion on ryanodine binding and Ca2+ uptake of cardiac sarcoplasmic reticulum. J Mol Cell Cardiol. 1995; 27: 1965–1975.[CrossRef][Medline] [Order article via Infotrieve]
28. Chakraborti T, Gosh SK, Michael JR, Batabyl SK, Chakraborti S. Targets of oxidative stress in cardiovascular system. Mol Cell Biochem. 1998; 187: 1–10.[CrossRef][Medline] [Order article via Infotrieve]
29. Davidge ST, Baker PN, Laughlin MK, Roberts JM. Nitric oxide produced by endothelial cells increases production of eicosanoids through activation of prostaglandin H synthase. Circ Res. 1995; 77: 274–283.
30. Stoos BA, Garvin JL. Actions of nitric oxide on renal epithelial transport. Clin Exp Pharmacol Physiol. 1997; 24: 591–594.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  L. Kopkan, M. A. H. Khan, A. Lis, M. S. Awayda, and D. S. A. Majid Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats Am J Physiol Renal Physiol, December 1, 2009; 297(6): F1606 - F1613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Matavelli, P. J. Kadowitz, L. G. Navar, and D. S. A. Majid Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats Am J Physiol Renal Physiol, January 1, 2009; 296(1): F170 - F176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shahid, J. Francis, and D. S. A. Majid Tumor necrosis factor-{alpha} induces renal vasoconstriction as well as natriuresis in mice Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1836 - F1844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Z. Haque and D. S. A. Majid Reduced renal responses to nitric oxide synthase inhibition in mice lacking the gene for gp91phox subunit of NAD(P)H oxidase Am J Physiol Renal Physiol, September 1, 2008; 295(3): F758 - F764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Just, C. L. Whitten, and W. J. Arendshorst Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors Am J Physiol Renal Physiol, April 1, 2008; 294(4): F719 - F728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Garvin and N. J. Hong Cellular Stretch Increases Superoxide Production in the Thick Ascending Limb Hypertension, February 1, 2008; 51(2): 488 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Soodvilai, Z. Jia, and T. Yang Hydrogen peroxide stimulates chloride secretion in primary inner medullary collecting duct cells via mPGES-1-derived PGE2 Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1571 - F1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wesseling, J. A. Joles, H. van Goor, H. A. Bluyssen, P. Kemmeren, F. C. Holstege, H. A. Koomans, and B. Braam Transcriptome-based identification of pro- and antioxidative gene expression in kidney cortex of nitric oxide-depleted rats Physiol Genomics, January 17, 2007; 28(2): 158 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Just, A. J. M. Olson, C. L. Whitten, and W. J. Arendshorst Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H83 - H92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Silva, P. A. Ortiz, N. J. Hong, and J. L. Garvin Superoxide Stimulates NaCl Absorption in the Thick Ascending Limb Via Activation of Protein Kinase C Hypertension, September 1, 2006; 48(3): 467 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. K. Dutta, J. Lane, L. J. Roberts II, and D. S. A. Majid Superoxide formation and interaction with nitric oxide modulate systemic arterial pressure and renal function in salt-depleted dogs. Experimental Biology and Medicine, March 1, 2006; 231(3): 269 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopkan and D. S.A. Majid Enhanced Superoxide Activity Modulates Renal Function in NO-Deficient Hypertensive Rats Hypertension, March 1, 2006; 47(3): 568 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Modlinger, T. Chabrashvili, P. S. Gill, M. Mendonca, D. G. Harrison, K. K. Griendling, M. Li, J. Raggio, A. Wellstein, Y. Chen, et al. RNA Silencing In Vivo Reveals Role of p22phox in Rat Angiotensin Slow Pressor Response Hypertension, February 1, 2006; 47(2): 238 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Juncos, N. J. Hong, and J. L. Garvin Differential effects of superoxide on luminal and basolateral Na+/H+ exchange in the thick ascending limb Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R79 - R83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Patel, Y. Chen, K. Dennehy, J. Blau, S. Connors, M. Mendonca, M. Tarpey, M. Krishna, J. B. Mitchell, W. J. Welch, et al. Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R37 - R43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. E. Lau, J. J. Galligan, D. L. Kreulen, and G. D. Fink Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R90 - R95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Takeda, H. Nishimatsu, E. Suzuki, H. Satonaka, D. Nagata, S. Oba, M. Sata, M. Takahashi, Y. Yamamoto, Y. Terauchi, et al. Ghrelin Improves Renal Function in Mice with Ischemic Acute Renal Failure J. Am. Soc. Nephrol., January 1, 2006; 17(1): 113 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopkan, A. Castillo, L. G. Navar, and D. S. A. Majid Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats Am J Physiol Renal Physiol, January 1, 2006; 290(1): F80 - F86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. de Richelieu, C. M. Sorensen, N.-H. Holstein-Rathlou, and M. Salomonsson NO-independent mechanism mediates tempol-induced renal vasodilation in SHR Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1227 - F1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopkan and D. S. A. Majid Superoxide Contributes to Development of Salt Sensitivity and Hypertension Induced by Nitric Oxide Deficiency Hypertension, October 1, 2005; 46(4): 1026 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-F. Xia, G. Bledsoe, L. Chao, and J. Chao Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats Am J Physiol Renal Physiol, September 1, 2005; 289(3): F622 - F631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Herrera and J. L. Garvin Recent Advances in the Regulation of Nitric Oxide in the Kidney Hypertension, June 1, 2005; 45(6): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Juncos and J. L. Garvin Superoxide enhances Na-K-2Cl cotransporter activity in the thick ascending limb Am J Physiol Renal Physiol, May 1, 2005; 288(5): F982 - F987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. A. Majid, A. Nishiyama, K. E. Jackson, and A. Castillo Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs Am J Physiol Renal Physiol, February 1, 2005; 288(2): F412 - F419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Varela, M. Herrera, and J. L. Garvin Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2- and is diminished by a high-salt diet Am J Physiol Renal Physiol, August 1, 2004; 287(2): F224 - F230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. A. Majid, A. Nishiyama, K. E. Jackson, and A. Castillo Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R27 - R32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Z. Haque and D. S. A. Majid Assessment of Renal Functional Phenotype in Mice Lacking gp91PHOX Subunit of NAD(P)H Oxidase Hypertension, February 1, 2004; 43(2): 335 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Brands, T. D. Bell, and B. Gibson Nitric Oxide May Prevent Hypertension Early in Diabetes by Counteracting Renal Actions of Superoxide Hypertension, January 1, 2004; 43(1): 57 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lopez, M. G. Salom, B. Arregui, F. Valero, and F. J. Fenoy Role of Superoxide in Modulating the Renal Effects of Angiotensin II Hypertension, December 1, 2003; 42(6): 1150 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shokoji, A. Nishiyama, Y. Fujisawa, H. Hitomi, H. Kiyomoto, N. Takahashi, S. Kimura, M. Kohno, and Y. Abe Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats Hypertension, February 1, 2003; 41(2): 266 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Ortiz and J. L. Garvin Superoxide stimulates NaCl absorption by the thick ascending limb Am J Physiol Renal Physiol, November 1, 2002; 283(5): F957 - F962. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||