(Hypertension. 1995;25:663-673.)
© 1995 American Heart Association, Inc.
Articles |
The Renal Medulla and Hypertension
From the Department of Physiology, Medical College of Wisconsin, Milwaukee.
Correspondence to Allen W. Cowley, Jr, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, PO Box 26509, Milwaukee, WI 53226-0509.
Abstract We review evidence supporting the conclusion that renal dysfunction underlies the development of all forms of hypertension in humans and experimental animals. Indexes of global renal function are generally normal in the early stages of most genetic forms of hypertension, but renal function is clearly impaired in long-established hypertension. Studies in our laboratory over the past decade summarized below have established that the renal medulla plays an important role in sodium and water homeostasis and in the long-term control of arterial pressure. Development of implanted optical fibers for measurement of cortical and medullary blood flows with laser-Doppler flowmetry and techniques for delivery of vasoactive compounds into the medullary interstitial space enabled us to examine determinants of medullary flow (nitric oxide, atrial natriuretic peptides, kinins, eicosanoids, vasopressin, renal sympathetic nerves, etc). We have shown in spontaneously hypertensive rats that the initial changes of renal function begin as a reduction of medullary blood flow in the absence of changes of cortical flow. Long-term medullary interstitial infusion of captopril, which preferentially increased medullary blood flow, resulted in a lowering of arterial pressure. In normal Sprague-Dawley rats, selective reduction of medullary flow with medullary interstitial or intravenous infusion of small amounts of NG-nitro-L-arginine methyl ester resulted in hypertension. These and other studies we review show that although blood flow to the inner renal medulla comprises less than 1% of the total renal blood flow, changes in flow to this region can have a major effect on sodium and water homeostasis and on the long-term control of arterial blood pressure.
Key Words: kidney medulla • hypertension, renal • laser-Doppler flowmetry • captopril
This article has been cited by other articles:
 |
|
 |
|
  N. Li, L. Chen, F. Yi, M. Xia, and P.-L. Li Salt-Sensitive Hypertension Induced by Decoy of Transcription Factor Hypoxia-Inducible Factor-1{alpha} in the Renal Medulla Circ. Res., May 9, 2008; 102(9): 1101 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tiwari, N. Sharma, P. S. Gill, P. Igarashi, C. R. Kahn, J. B. Wade, and C. M. A. Ecelbarger Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor PNAS, April 29, 2008; 105(17): 6469 - 6474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Spurgeon-Pechman, D. L. Donohoe, D. L. Mattson, H. Lund, L. James, and D. P. Basile Recovery from acute renal failure predisposes hypertension and secondary renal disease in response to elevated sodium Am J Physiol Renal Physiol, July 1, 2007; 293(1): F269 - F278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Luft Vasopressin, Urine Concentration, and Hypertension: A New Perspective on an Old Story Clin. J. Am. Soc. Nephrol., March 1, 2007; 2(2): 196 - 197. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Williams, A. Sarkis, B. Lopez, R. P. Ryan, A. K. Flasch, and R. J. Roman Elevations in Renal Interstitial Hydrostatic Pressure and 20-Hydroxyeicosatetraenoic Acid Contribute to Pressure Natriuresis Hypertension, March 1, 2007; 49(3): 687 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Rajapakse, G. A. Eppel, R. E. Widdop, and R. G. Evans ANG II type 2 receptors and neural control of intrarenal blood flow Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1669 - R1676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Guo and T. Yang Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion. Experimental Biology and Medicine, June 1, 2006; 231(6): 1001 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. K. Leong, L. E. Yang, C. S. Landon, A. A. McDonough, and K.-P. Yip Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1543 - F1550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Prasad Functional MRI of the kidney: tools for translational studies of pathophysiology of renal disease Am J Physiol Renal Physiol, May 1, 2006; 290(5): F958 - F974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vargas, J. M. Moreno, I. Rodriguez-Gomez, R. Wangensteen, A. Osuna, M. Alvarez-Guerra, and J. Garcia-Estan Vascular and renal function in experimental thyroid disorders Eur. J. Endocrinol., February 1, 2006; 154(2): 197 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Rajapakse, A. K. Sampson, G. A. Eppel, and R. G. Evans Angiotensin II and nitric oxide in neural control of intrarenal blood flow Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2005; 289(3): R745 - R754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Rodriguez-Gomez, R. Wangensteen, J. M. Moreno, V. Chamorro, A. Osuna, and F. Vargas Effects of chronic inhibition of inducible nitric oxide synthase in hyperthyroid rats Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1252 - E1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zewde and D. L. Mattson Inhibition of Cyclooxygenase-2 in the Rat Renal Medulla Leads to Sodium-Sensitive Hypertension Hypertension, October 1, 2004; 44(4): 424 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Schlenker, C. K. Kost Jr., and M. M. Likness Effects of long-term captopril and L-arginine treatment on ventilation and blood pressure in obese male SHHF rats J Appl Physiol, September 1, 2004; 97(3): 1032 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Smallegange, T. M. Hale, T. L. Bushfield, and M. A. Adams Persistent Lowering of Pressure by Transplanting Kidneys From Adult Spontaneously Hypertensive Rats Treated With Brief Antihypertensive Therapy Hypertension, July 1, 2004; 44(1): 89 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Oparil, M. A. Zaman, and D. A. Calhoun Pathogenesis of Hypertension Ann Intern Med, November 4, 2003; 139(9): 761 - 776. [Full Text] [PDF]
|
|
|
|
|
|
I. Rodriguez-Gomez, J. Sainz, R. Wangensteen, J. M. Moreno, J. Duarte, A. Osuna, and F. Vargas Increased Pressor Sensitivity to Chronic Nitric Oxide Deficiency in Hyperthyroid Rats Hypertension, August 1, 2003; 42(2): 220 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fenton, C.-L. Chou, S. Ageloff, W. Brandt, J. B. Stokes, and M. A. Knepper Increased collecting duct urea transporter expression in Dahl salt-sensitive rats Am J Physiol Renal Physiol, July 1, 2003; 285(1): F143 - F151. [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]
|
|
|
|
|
|
I. Vassileva, C. Mountain, and D. M. Pollock Functional Role of ETB Receptors in the Renal Medulla Hypertension, June 1, 2003; 41(6): 1359 - 1363. [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]
|
|
|
|
|
|
A. J. Dahly, K. M. Hoagland, A. K. Flasch, S. Jha, S. R. Ledbetter, and R. J. Roman Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R757 - R767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Johnson, J. Herrera-Acosta, G. F. Schreiner, and B. Rodriguez-Iturbe Subtle Acquired Renal Injury as a Mechanism of Salt-Sensitive Hypertension N. Engl. J. Med., March 21, 2002; 346(12): 913 - 923. [Full Text] [PDF]
|
|
|
|
|
|
M.-G. Feng, S. A. W. Dukacz, and R. L. Kline Selective effect of tempol on renal medullary hemodynamics in spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1420 - R1425. [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]
|
|
|
|
|
|
R. C. Harris and M. D. Breyer Physiological regulation of cyclooxygenase-2 in the kidney Am J Physiol Renal Physiol, July 1, 2001; 281(1): F1 - F11. [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]
|
|
|
|
|
|
D. S. A. Majid, K. E. Said, S. A. Omoro, and L. G. Navar Nitric Oxide Dependency of Arterial Pressure-Induced Changes in Renal Interstitial Hydrostatic Pressure in Dogs Circ. Res., February 16, 2001; 88(3): 347 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-P. Zou, N. Li, and A. W. Cowley Jr. Production and Actions of Superoxide in the Renal Medulla Hypertension, February 1, 2001; 37(2): 547 - 553. [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]
|
|
|
|
 |
|
 B. Nafz, J. Stegemann, M. H. Bestle, N. Richter, E. Seeliger, I. Schimke, H. W. Reinhardt, and P. B. Persson Antihypertensive Effect of 0.1-Hz Blood Pressure Oscillations to the Kidney Circulation, February 8, 2000; 101(5): 553 - 557. [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. Szentivanyi Jr, A.-P. Zou, C. Y. Maeda, D. L. Mattson, and A. W. Cowley Jr Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension Hypertension, January 1, 2000; 35(1): 418 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Correia, G. Bergstrom, A. J. Lawrence, and R. G. Evans Renal medullary interstitial infusion of norepinephrine in anesthetized rabbits: methodological considerations Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1999; 277(1): R112 - R122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. GROSS, W. SCHNEIDER, W.-H. SCHUNCK, E. MERVAALA, and F. C. LUFT Chronic Effects of Lovastatin and Bezafibrate on Cortical and Medullary Hemodynamics in Deoxycorticosterone Acetate-Salt Hypertensive Mice J. Am. Soc. Nephrol., July 1, 1999; 10(7): 1430 - 1439. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. W. Dukacz, M. A. Adams, and R. L. Kline Short- and long-term enalapril affect renal medullary hemodynamics in the spontaneously hypertensive rat Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R10 - R16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhuo, M. Ohishi, and F. A. O. Mendelsohn Roles of AT1 and AT2 Receptors in the Hypertensive Ren-2 Gene Transgenic Rat Kidney Hypertension, January 1, 1999; 33(1): 347 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Cowley Jr., M. M. Skelton, and T. M. Kurth Effects of long-term vasopressin receptor stimulation on medullary blood flow and arterial pressure Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1420 - R1424. [Abstract] [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]
|
|
|
|
|
|
G. Bergstrom and R. G. Evans Effects of renal medullary infusion of a vasopressin V1 agonist on renal antihypertensive mechanisms in rabbits Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1998; 275(1): R76 - R85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gross, T. M. Kurth, M. M. Skelton, D. L. Mattson, and A. W. Cowley Jr. Effects of daily sodium intake and ANG II on cortical and medullary renal blood flow in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1998; 274(5): R1317 - R1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Edwards and T. L. Pallone A multiunit model of solute and water removal by inner medullary vasa recta Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1202 - H1210. [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]
|
|
|
|
|
|
M. Tanaka, O. Schmidlin, S.-L. Yi, A. W. Bollen, and R. C. Morris Jr. Genetically determined chloride-sensitive hypertension and stroke PNAS, December 23, 1997; 94(26): 14748 - 14752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Kone A `BOLD' New Approach to Renal Oxygen Economy Circulation, December 15, 1996; 94(12): 3067 - 3068. [Full Text]
|
|
|
|
|
|
M. C. Ortiz, N. M. Atucha, V. Lahera, F. Vargas, T. Quesada, and J. Garcia-Estan Importance of Nitric Oxide and Prostaglandins in the Control of Rat Renal Papillary Blood Flow Hypertension, March 1, 1996; 27(3): 377 - 381. [Abstract] [Full Text]
|
|