(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
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
This article has been cited by other articles:
 |
|
 |
|
  C. Jin, C. Hu, A. Polichnowski, T. Mori, M. Skelton, S. Ito, and A. W. Cowley Jr Effects of Renal Perfusion Pressure on Renal Medullary Hydrogen Peroxide and Nitric Oxide Production Hypertension, June 1, 2009; 53(6): 1048 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Cowley Jr Renal Medullary Oxidative Stress, Pressure-Natriuresis, and Hypertension Hypertension, November 1, 2008; 52(5): 777 - 786. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Abassi, B. Bishara, T. Karram, S. Khatib, J. Winaver, and A. Hoffman Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R842 - R850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Palm, M. Friederich, P.-O. Carlsson, P. Hansell, T. Teerlink, and P. Liss Reduced nitric oxide in diabetic kidneys due to increased hepatic arginine metabolism: implications for renomedullary oxygen availability Am J Physiol Renal Physiol, January 1, 2008; 294(1): F30 - F37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Pollock and P. K. Carmines Diabetic nephropathy: nitric oxide and renal medullary hypoxia Am J Physiol Renal Physiol, January 1, 2008; 294(1): F28 - F29. [Full Text] [PDF]
|
|
|
|
 |
|
 E. O'Riordan, N. Mendelev, S. Patschan, D. Patschan, J. Eskander, L. Cohen-Gould, P. Chander, and M. S. Goligorsky Chronic NOS inhibition actuates endothelial-mesenchymal transformation Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H285 - H294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Li, F. Yi, E. A. dos Santos, D. K. Donley, and P.-L. Li Role of Renal Medullary Heme Oxygenase in the Regulation of Pressure Natriuresis and Arterial Blood Pressure Hypertension, January 1, 2007; 49(1): 148 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yang, A. Zhang, A. Pasumarthy, L. Zhang, Z. Warnock, and J. B. Schnermann Nitric oxide stimulates COX-2 expression in cultured collecting duct cells through MAP kinases and superoxide but not cGMP Am J Physiol Renal Physiol, October 1, 2006; 291(4): F891 - F895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Palm, D. G. Buerk, P.-O. Carlsson, P. Hansell, and P. Liss Reduced Nitric Oxide Concentration in the Renal Cortex of Streptozotocin-Induced Diabetic Rats: Effects on Renal Oxygenation and Microcirculation Diabetes, November 1, 2005; 54(11): 3282 - 3287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Oyekan Differential Effects of 20-Hydroxyeicosatetraenoic Acid on Intrarenal Blood Flow in the Rat J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1289 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, K. Rhinehart, G. Solis, J. Pittner, W. Lee-Kwon, W. J. Welch, C. S. Wilcox, and T. L. Pallone Chronic ANG II infusion increases NO generation by rat descending vasa recta Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H29 - H36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kakoki, H.-S. Kim, W. J. Arendshorst, and D. L. Mattson L-Arginine uptake affects nitric oxide production and blood flow in the renal medulla Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1478 - R1485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, T. Pibulsonggram, and A. Edwards Determinants of basal nitric oxide concentration in the renal medullary microcirculation Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1189 - F1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pouvreau, B. Allard, C. Berthier, and V. Jacquemond Control of intracellular calcium in the presence of nitric oxide donors in isolated skeletal muscle fibres from mouse J. Physiol., November 1, 2004; 560(3): 779 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 B. Li, J. Yao, T. Morioka, and T. Oite Nitric Oxide Increases Albumin Permeability of Isolated Rat Glomeruli via a Phosphorylation-Dependent Mechanism J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2616 - 2624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liang, T. J. Berndt, and F. G. Knox Mechanism underlying diuretic effect of L-NAME at a subpressor dose Am J Physiol Renal Physiol, September 1, 2001; 281(3): F414 - F419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-P. ZOU, Z.-Z. YANG, P.-L. LI, and A. W. COWLEY JR. Oxygen-dependent expression of hypoxia-inducible factor-1{alpha} in renal medullary cells of rats Physiol Genomics, August 28, 2001; 6(3): 159 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kakoki, A.-P. Zou, and D. L. Mattson The influence of nitric oxide synthase 1 on blood flow and interstitial nitric oxide in the kidney Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R91 - R97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Rhinehart and T. L. Pallone Nitric oxide generation by isolated descending vasa recta Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H316 - H324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. W. Dukacz, M.-G. Feng, L.-F. Yang, R. M. K. W. Lee, and R. L. Kline Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R1076 - R1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-P. Zou and A. W. Cowley Jr. alpha 2-Adrenergic receptor-mediated increase in NO production buffers renal medullary vasoconstriction Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R769 - R777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Solhaug, X. Q. Dong, R. D. Adelman, and K.-W. Dong Ontogeny of neuronal nitric oxide synthase, NOS I, in the developing porcine kidney Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1453 - R1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Wu, B. Cholewa, and D. L. Mattson Characterization of L-arginine transporters in rat renal inner medullary collecting duct Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1506 - R1512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liang and F. G. Knox Production and functional roles of nitric oxide in the proximal tubule Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1117 - R1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hoffman, Z. A. Abassi, S. Brodsky, R. Ramadan, and J. Winaver Mechanisms of Big Endothelin-1-Induced Diuresis and Natriuresis : Role of ETB Receptors Hypertension, March 1, 2000; 35(3): 732 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Szentivanyi Jr, F. Park, C. Y. Maeda, and A. W. Cowley Jr Nitric Oxide in the Renal Medulla Protects From Vasopressin-Induced Hypertension Hypertension, March 1, 2000; 35(3): 740 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-P. Zou, H. Billington, N. Su, and A. W. Cowley Jr Expression and Actions of Heme Oxygenase in the Renal Medulla of Rats Hypertension, January 1, 2000; 35(1): 342 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liang and F. G. Knox Nitric oxide activates PKCalpha and inhibits Na+-K+-ATPase in opossum kidney cells Am J Physiol Renal Physiol, December 1, 1999; 277(6): F859 - F865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Reaux, M. C. Fournie-Zaluski, C. David, S. Zini, B. P. Roques, P. Corvol, and C. Llorens-Cortes Aminopeptidase A inhibitors as potential central antihypertensive agents PNAS, November 9, 1999; 96(23): 13415 - 13420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. MATSUDA, K. HAYASHI, K. ARAKAWA, M. NAITOH, E. KUBOTA, M. HONDA, A. MATSUMOTO, H. SUZUKI, T. YAMAMOTO, F. KAJIYA, et al. Zonal Heterogeneity in Action of Angiotensin-Converting Enzyme Inhibitor on Renal Microcirculation: Role of Intrarenal Bradykinin J. Am. Soc. Nephrol., November 1, 1999; 10(11): 2272 - 2282. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Sener and F. G. Smith Acetylcholine chloride and renal hemodynamics during postnatal maturation in conscious lambs J Appl Physiol, October 1, 1999; 87(4): 1296 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Pflueger, T. S. Larson, S. Hagl, and F. G. Knox Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R725 - R733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yang, D. Sun, Y. G. Huang, A. Smart, J. P. Briggs, and J. B. Schnermann Differential regulation of COX-2 expression in the kidney by lipopolysaccharide: role of CD14 Am J Physiol Renal Physiol, July 1, 1999; 277(1): F10 - F16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Braam Renal endothelial and macula densa NOS: integrated response to changes in extracellular fluid volume Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1999; 276(6): R1551 - R1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Mupanomunda, N. Ishioka, and R. D. Bukoski Interstitial Ca2+ undergoes dynamic changes sufficient to stimulate nerve-dependent Ca2+-induced relaxation Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H1035 - H1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Omoro, D. S. A. Majid, S. S. El-Dahr, and L. G. Navar Kinin influences on renal regional blood flow responses to angiotensin-converting enzyme inhibition in dogs Am J Physiol Renal Physiol, February 1, 1999; 276(2): F271 - F277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Miyata and A. W. Cowley Jr Renal Intramedullary Infusion of L-Arginine Prevents Reduction of Medullary Blood Flow and Hypertension in Dahl Salt-Sensitive Rats Hypertension, January 1, 1999; 33(1): 446 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zatz and C. Baylis Chronic Nitric Oxide Inhibition Model Six Years On Hypertension, December 1, 1998; 32(6): 958 - 964. [Full Text] [PDF]
|
|
|
|
|
|
N. Miyata, A. P. Zou, D. L. Mattson, and A. W. Cowley Jr. Renal medullary interstitial infusion of L-arginine prevents hypertension in Dahl salt-sensitive rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1667 - R1673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Park, A.-P. Zou, and A. W. Cowley Jr Arginine Vasopressin–Mediated Stimulation of Nitric Oxide Within the Rat Renal Medulla Hypertension, November 1, 1998; 32(5): 896 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alonso-Galicia, C.-W. Sun, J. R. Falck, D. R. Harder, and R. J. Roman Contribution of 20-HETE to the vasodilator actions of nitric oxide in renal arteries Am J Physiol Renal Physiol, September 1, 1998; 275(3): F370 - F378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Roczniak, J. Zimpelmann, and K. D. Burns Effect of dietary salt on neuronal nitric oxide synthase in the inner medullary collecting duct Am J Physiol Renal Physiol, July 1, 1998; 275(1): F46 - F54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Abassi, K. Gurbanov, I. Rubinstein, O. S. Better, A. Hoffman, and J. Winaver Regulation of intrarenal blood flow in experimental heart failure: role of endothelin and nitric oxide Am J Physiol Renal Physiol, April 1, 1998; 274(4): F766 - F774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-P. Zou, F. Wu, and A. W. Cowley Jr Protective Effect of Angiotensin II-Induced Increase in Nitric Oxide in the Renal Medullary Circulation Hypertension, January 1, 1998; 31(1): 271 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nishiyama, S. Kimura, T. Fukui, M. Rahman, H. Yoneyama, H. Kosaka, and Y. Abe Blood flow-dependent changes in renal interstitial guanosine 3',5'-cyclic monophosphate in rabbits Am J Physiol Renal Physiol, February 1, 2002; 282(2): F238 - F244. [Abstract] [Full Text] [PDF]
|
|