| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
WATER AND ELECTROLYTE HOMEOSTASIS
Departments of 1Genome Science, 2Molecular Genetics, Biochemistry, and Microbiology, and 3Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; and 4Department of Biological Sciences, Northern Kentucky University, Highland Heights, Kentucky
Submitted 29 March 2004 ; accepted in final form 12 November 2004
NHE3 Na+/H+ exchanger knockout (Nhe3–/–) mice have severe absorptive deficits in the kidney proximal tubule and intestinal tract. The resulting hypovolemia has confounded efforts to carefully evaluate the specific effects of NHE3 deficiency on kidney function. Development of mice with transgenic expression of NHE3 in the small intestine (tgNhe3–/–) has allowed us to analyze the role of renal NHE3 in overall maintenance of blood pressure, pressure natriuresis, and autoregulation of both glomerular filtration rate (GFR) and renal blood flow (RBF). Ambulatory blood pressure, measured by telemetry, was lower in tgNhe3–/– mice than in wild-type controls (tgNhe3+/+) when the mice were maintained on a normal NaCl diet but was normalized when they were provided with a high NaCl intake. Furthermore, administration of the AT1-receptor blocker losartan showed that circulating ANG II plays a major role in maintaining blood pressure in tgNhe3–/– mice fed normal NaCl but not in those receiving high NaCl. Clearance studies revealed a blunted pressure-natriuresis response in tgNhe3–/– mice at lower blood pressures but a robust response at higher blood pressures. Autoregulation of GFR and RBF was normal in tgNhe3–/– mice. These results show that dietary NaCl loading normalizes blood pressure in awake tgNhe3–/– mice and that alterations in NHE3 activity are not essential for normal autoregulation of GFR and RBF. Furthermore, the data strongly support the hypothesis that NHE3 plays an important role in the diuretic and natriuretic responses to increases in blood pressure but also show that mechanisms not involving NHE3 mediate pressure natriuresis in the higher range of blood pressures studied.
telemetry; pressure natriuresis; autoregulation; Slc9a3; renal blood flow; glomerular filtration rate
This article has been cited by other articles:
|
|
 |
|
  R. D. Rudic and D. J. Fulton Pressed for time: the circadian clock and hypertension J Appl Physiol, October 1, 2009; 107(4): 1328 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Donowitz, S. Mohan, C. X. Zhu, T.-E Chen, R. Lin, B. Cha, N. C. Zachos, R. Murtazina, R. Sarker, and X. Li NHE3 regulatory complexes J. Exp. Biol., June 1, 2009; 212(11): 1638 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. C. Li and J. L. Zhuo Selective knockdown of AT1 receptors by RNA interference inhibits Val5-ANG II endocytosis and NHE-3 expression in immortalized rabbit proximal tubule cells Am J Physiol Cell Physiol, July 1, 2007; 293(1): C367 - C378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sandu, F. Artunc, M. Palmada, R. Rexhepaj, F. Grahammer, A. Hussain, C. Yun, D. R. Alessi, and F. Lang Impaired intestinal NHE3 activity in the PDK1 hypomorphic mouse Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G868 - G876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Mullins, M. A. Bailey, and J. J. Mullins Hypertension, Kidney, and Transgenics: A Fresh Perspective Physiol Rev, April 1, 2006; 86(2): 709 - 746. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
