| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of 1Pathology and Laboratory Medicine and of 2Cellular and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina; 3Department of Pediatrics, University of Virginia, Charlottesville, Virginia; and 4Siberian Division, Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia
Submitted 20 June 2005 ; accepted in final form 5 August 2005
To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS+/+, AS+/–, and AS–/– mice. AS+/– mice have normal blood pressures and show no abnormalities in electrolytes or kidney gene expression, but they have significantly higher than normal urine volume and lower urine osmolality. In contrast, the AS–/– mice have low blood pressure, abnormal electrolyte homeostasis (increased plasma concentrations of K+, Ca2+, and Mg2+ and decreased concentrations of HCO3– and Cl– but no difference in the plasma Na+ level), and disturbances in water metabolism (higher urine output, decreased urine osmolality, and impaired urine concentrating and diluting ability). Absence of aldosterone in the AS–/– mice induced several compensatory changes: an increased food intake-to-body weight ratio, an elevated plasma concentration of glucocorticoids, and strong activation of the renin-angiotensin system. Parallel with the markedly increased synthesis and release of renin, the AS–/– mice showed increased expression of cyclooxygenase-2 (COX-2) in macula densa. On salt supplementation, plasma electrolyte concentrations and kidney renin and COX-2 levels became similar to those of wild-type mice, but the lower blood pressure of the AS–/– mice was not corrected. Thus absence of aldosterone in AS–/– mice results in impairment of Na+ reabsorption in the distal nephron, decreased blood pressure, and strong renin-angiontensin system activation. Our data show the substantial correction of these abnormalities, except the low blood pressure, by high dietary salt does not depend on aldosterone.
aldosterone synthase; blood pressure; electrolytes; renin; cyclooxygenase-2
This article has been cited by other articles:
|
|
 |
|
  C. Wagner, C. de Wit, M. Gerl, A. Kurtz, and K. Hocherl Increased expression of cyclooxygenase 2 contributes to aberrant renin production in connexin 40-deficient kidneys Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1781 - R1786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stubbe, K. Madsen, F. T. Nielsen, R. K. Bonde, O. Skott, and B. L. Jensen Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury Am J Physiol Renal Physiol, September 1, 2007; 293(3): F780 - F789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Makhanova, M. L.S. Sequeira-Lopez, R. A. Gomez, H.-S. Kim, and O. Smithies Disturbed Homeostasis in Sodium-Restricted Mice Heterozygous and Homozygous for Aldosterone Synthase Gene Disruption Hypertension, December 1, 2006; 48(6): 1151 - 1159. [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 |
