| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Division of Nephrology, University of Washington Medical Center, Seattle, Washington 98195; 2 Department of Physiology, University of Florida, Gainesville, Florida 32610; 3 Center for Molecular Physiology Research, Children's Research Institute, Washington, District of Columbia 20010; 4 Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina 27599-7545; 5 Departamento de Ciencias Fisiologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile; and 6 Division of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710 Korea
We investigated the hypothesis that hypokalemia might induce renal injury via a mechanism that involves subtle renal injury and alterations in local vasoactive mediators that would favor sodium retention. To test this hypothesis, we conducted studies in rats with diet-induced K+ deficiency. We also determined whether rats with hypokalemic nephropathy show salt sensitivity. Twelve weeks of hypokalemia resulted in a decrease in creatinine clearance, tubulointerstitial injury with macrophage infiltration, interstitial collagen type III deposition, and an increase in osteopontin expression (a tubular marker of injury). The renal injury was greatest in the outer medulla with radiation into the cortex, suggestive of an ischemic etiology. Consistent with this hypothesis, we found an increased uptake of a hypoxia marker, pimonidazole, in the cortex. The intrarenal injury was associated with increased cortical angiontensin-converting enzyme (ACE) expression and continued cortical angiotensin II generation despite systemic suppression of the renin-angiotensin system, an increase in renal endothelin-1, a decrease in renal kallikrein, and a decrease in urinary nitrite/nitrates and prostaglandin E2 excretion. At 12 wk, hypokalemic rats were placed on a normal-K+ diet with either high (4%)- or low (0.01%)-NaCl content. Despite correction of hypokalemia and normalization of renal function, previously hypokalemic rats showed an elevated blood pressure in response to a high-salt diet compared with normokalemic controls. Hypokalemia is associated with alterations in vasoactive mediators that favor intrarenal vasoconstriction and an ischemic pattern of renal injury. These alterations may predispose the animals to salt-sensitive hypertension that manifests despite normalization of the serum K+.
angiotensin II; endothelin; kallikrein; hypertension
This article has been cited by other articles:
|
|
 |
|
  H. Gil-Pena, E. Garcia-Lopez, O. Alvarez-Garcia, V. Loredo, E. Carbajo-Perez, F. A. Ordonez, J. Rodriguez-Suarez, and F. Santos Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment Am J Physiol Renal Physiol, September 1, 2009; 297(3): F639 - F645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Reungjui, C. A. Roncal, W. Sato, O. Y. Glushakova, B. P. Croker, S.-i. Suga, X. Ouyang, K. Tungsanga, T. Nakagawa, R. J. Johnson, et al. Hypokalemic Nephropathy is Associated with Impaired Angiogenesis J. Am. Soc. Nephrol., January 1, 2008; 19(1): 125 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. S. Jeon, K.-H. Han, S.-H. Park, S. D. Lee, M. R. Sheen, J.-Y. Jung, W. Y. Kim, J. M. Sands, J. Kim, and H. M. Kwon Downregulation of renal TonEBP in hypokalemic rats Am J Physiol Renal Physiol, July 1, 2007; 293(1): F408 - F415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Villanueva, C. Cespedes, and C. P. Vio Ischemic acute renal failure induces the expression of a wide range of nephrogenic proteins Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R861 - R870. [Abstract] [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]
|
|
|
|
|
|
D. P. Basile, K. Fredrich, M. Alausa, C. P. Vio, M. Liang, M. R. Rieder, A. S. Greene, and A. W. Cowley Jr. Identification of persistently altered gene expression in the kidney after functional recovery from ischemic acute renal failure Am J Physiol Renal Physiol, May 1, 2005; 288(5): F953 - F963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-X. Wang and P. W. Sanders Mechanism of hypertensive nephropathy in the Dahl/Rapp rat: a primary disorder of vascular smooth muscle Am J Physiol Renal Physiol, January 1, 2005; 288(1): F236 - F242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Matsumoto, T. Tanaka, T. Yamamoto, E. Noiri, T. Miyata, R. Inagi, T. Fujita, and M. Nangaku Hypoperfusion of Peritubular Capillaries Induces Chronic Hypoxia before Progression of Tubulointerstitial Injury in a Progressive Model of Rat Glomerulonephritis J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1574 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Manotham, T. Tanaka, M. Matsumoto, T. Ohse, T. Miyata, R. Inagi, K. Kurokawa, T. Fujita, and M. Nangaku Evidence of Tubular Hypoxia in the Early Phase in the Remnant Kidney Model J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1277 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Suga, N. Yasui, F. Yoshihara, T. Horio, Y. Kawano, K. Kangawa, and R. J. Johnson Endothelin A Receptor Blockade and Endothelin B Receptor Blockade Improve Hypokalemic Nephropathy by Different Mechanisms J. Am. Soc. Nephrol., February 1, 2003; 14(2): 397 - 406. [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]
|
|
|
|
|
|
D.-H. Kang, J. Kanellis, C. Hugo, L. Truong, S. Anderson, D. Kerjaschki, G. F. Schreiner, and R. J. Johnson Role of the Microvascular Endothelium in Progressive Renal Disease J. Am. Soc. Nephrol., March 1, 2002; 13(3): 806 - 816. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
