(Hypertension. 1999;34:151-159.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines
From the Division of Nephrology, University of Washington Medical Center, Seattle (R.J.J., K.L.G., S.S.), Section Immunology, Department of Internal Medicine, University of Maastricht, Netherlands (A.M.D.), and Division of Nephrology, Loyola University Medical Center, Maywood, Ill, and Hines Veteran Affairs Hospital, Hines, Ill (K.G., A.B.).
Correspondence to Richard J. Johnson, MD, Division of Nephrology, Box 356521, University of Washington Medical Center, Seattle WA 98195. E-mail nephrol{at}u.washington.edu
Abstract—We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor ß by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r2=0.99) and the degree of BP lability (r2=0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r2=0.74), and the final glomerular filtration rate (r2=0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged.
Key Words: phenylephrine • renal circulation • hypertension, episodic • sympathetic nervous system
This article has been cited by other articles:
 |
|
 |
|
  A. J. Polichnowski and A. W. Cowley Jr Pressure-Induced Renal Injury in Angiotensin II Versus Norepinephrine-Induced Hypertensive Rats Hypertension, December 1, 2009; 54(6): 1269 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Leonard, J. L. Friedrich, and D. P. Basile VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1648 - F1657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. K. Somers, D. P. White, R. Amin, W. T. Abraham, F. Costa, A. Culebras, S. Daniels, J. S. Floras, C. E. Hunt, L. J. Olson, et al. Sleep Apnea and Cardiovascular Disease: An American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health) Circulation, September 2, 2008; 118(10): 1080 - 1111. [Full Text] [PDF]
|
|
|
|
 |
|
 V. K. Somers, D. P. White, R. Amin, W. T. Abraham, F. Costa, A. Culebras, S. Daniels, J. S. Floras, C. E. Hunt, L. J. Olson, et al. Sleep Apnea and Cardiovascular Disease: An American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health) J. Am. Coll. Cardiol., August 19, 2008; 52(8): 686 - 717. [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Pechman, D. P. Basile, H. Lund, and D. L. Mattson Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1234 - R1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. de Boer, R. G. IJzerman, R. T. de Jongh, E. C. Eringa, C. D.A. Stehouwer, Y. M. Smulders, and E. H. Serne Birth Weight Relates to Salt Sensitivity of Blood Pressure in Healthy Adults Hypertension, April 1, 2008; 51(4): 928 - 932. [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]
|
|
|
|
|
|
M. Franco, F. Martinez, B. Rodriguez-Iturbe, R. J. Johnson, J. Santamaria, A. Montoya, T. Nepomuceno, R. Bautista, E. Tapia, and J. Herrera-Acosta Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1281 - F1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Weir Blood pressure salt sensitivity: a biomeasure of kidney disease susceptibility in diabetics? Nephrol. Dial. Transplant., October 1, 2005; 20(10): 2022 - 2024. [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Johnson, M. S. Segal, T. Srinivas, A. Ejaz, W. Mu, C. Roncal, L. G. Sanchez-Lozada, M. Gersch, B. Rodriguez-Iturbe, D.-H. Kang, et al. Essential Hypertension, Progressive Renal Disease, and Uric Acid: A Pathogenetic Link? J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1909 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Johnson, B. Rodriguez-Iturbe, T. Nakagawa, D.-H. Kang, D. I. Feig, and J. Herrera-Acosta Subtle Renal Injury Is Likely a Common Mechanism for Salt-Sensitive Essential Hypertension Hypertension, March 1, 2005; 45(3): 326 - 330. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Joles and H. A. Koomans Causes and Consequences of Increased Sympathetic Activity in Renal Disease Hypertension, April 1, 2004; 43(4): 699 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mori and A. W. Cowley Jr. Role of Pressure in Angiotensin II-Induced Renal Injury: Chronic Servo-Control of Renal Perfusion Pressure in Rats Hypertension, April 1, 2004; 43(4): 752 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Grisk and R. Rettig Interactions between the sympathetic nervous system and the kidneys in arterial hypertension Cardiovasc Res, February 1, 2004; 61(2): 238 - 246. [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]
|
|
|
|
|
|
A. B. Roald, J. Ofstad, and B. M. Iversen Attenuated buffering of renal perfusion pressure variation in juxtamedullary cortex in SHR Am J Physiol Renal Physiol, March 1, 2002; 282(3): F506 - F511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. FRANCO, E. TAPIA, J. SANTAMARIA, I. ZAFRA, R. GARCIA-TORRES, K. L. GORDON, H. PONS, B. RODRIGUEZ-ITURBE, R. J. JOHNSON, and J. HERRERA-ACOSTA Renal Cortical Vasoconstriction Contributes to Development of Salt-Sensitive Hypertension after Angiotensin II Exposure J. Am. Soc. Nephrol., November 1, 2001; 12(11): 2263 - 2271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-I. Suga, M. I. Phillips, P. E. Ray, J. A. Raleigh, C. P. Vio, Y.-G. Kim, M. Mazzali, K. L. Gordon, J. Hughes, and R. J. Johnson Hypokalemia induces renal injury and alterations in vasoactive mediators that favor salt sensitivity Am J Physiol Renal Physiol, October 1, 2001; 281(4): F620 - F629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Quiroz, H. Pons, K. L. Gordon, J. Rincon, M. Chavez, G. Parra, J. Herrera-Acosta, D. Gomez-Garre, R. Largo, J. Egido, et al. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition Am J Physiol Renal Physiol, July 1, 2001; 281(1): F38 - F47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Kang, Y.-G. Kim, T. F. Andoh, K. L. Gordon, S.-I. Suga, M. Mazzali, J. A. Jefferson, J. Hughes, W. Bennett, G. F. Schreiner, et al. Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular endothelial growth factor Am J Physiol Renal Physiol, April 1, 2001; 280(4): F727 - F736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chiolero, G. Wurzner, and M. Burnier Renal determinants of the salt sensitivity of blood pressure Nephrol. Dial. Transplant., March 1, 2001; 16(3): 452 - 458. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Asou, S. R. Rittling, H. Yoshitake, K. Tsuji, K. Shinomiya, A. Nifuji, D. T. Denhardt, and M. Noda Osteopontin Facilitates Angiogenesis, Accumulation of Osteoclasts, and Resorption in Ectopic Bone Endocrinology, March 1, 2001; 142(3): 1325 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Reddi, V. R. Nimmagadda, A. Lefkowitz, H.-R. Kuo, and J. S. Bollineni Effect of Antihypertensive Therapy on Renal Injury in Type 2 Diabetic Rats With Hypertension Hypertension, August 1, 2000; 36(2): 233 - 238. [Abstract] [Full Text] [PDF]
|
|