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Aldosterone concentrations vary in advanced chronic renal failure (CRF). The isozyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which confers aldosterone specificity for mineralocorticoid receptors in distal tubules and collecting ducts, has been reported to be decreased or normal in patients with renal diseases. Our objective was to determine the role of aldosterone and 11β-HSD2 renal microsome activity, normalized for glomerular filtration rate (GFR), in maintaining K+ homeostasis in 5/6 nephrectomized rats. Male Wistar rats weighing 180-220 g at the beginning of the study were used. Rats with experimental CRF obtained by 5/6 nephrectomy (N = 9) and sham rats (N = 10) were maintained for 4 months. Systolic blood pressure and plasma creatinine (Pcr) concentration were measured at the end of the experiment. Sodium and potassium excretion and GFR were evaluated before and after spironolactone administration (10 mg·kg -1·day-1 for 7 days) and 11β-HSD2 activity on renal microsomes was determined. Systolic blood pressure (means ± SEM; Sham = 105 ± 8 and CRF = 149 ± 10 mmHg) and Pcr (Sham = 0.42 ± 0.03 and CRF = 2.53 ± 0.26 mg/dL) were higher (P < 0.05) while GFR (Sham = 1.46 ± 0.26 and CRF = 0.61 ± 0.06 mL/min) was lower (P < 0.05) in CRF, and plasma aldosterone (Pald) was the same in the two groups. Urinary sodium and potassium excretion was similar in the two groups under basal conditions but, after spironolactone treatment, only potassium excretion was decreased in CRF rats (sham = 0.95 ± 0.090 (before) vs 0.89 ± 0.09 ?Eq/min (after) and CRF = 1.05 ± 0.05 (before) vs 0.37 ± 0.07 μEq/min (after); P < 0.05). 11β-HSD2 activity on renal microsomes was lower in CRF rats (sham = 0.807 ± 0.09 and CRF = 0.217 ± 0.07 nmol·min-1·mg protein-1; P < 0.05), although when normalized for mL GFR it was similar in both groups. We conclude that K+ homeostasis is maintained during CRF development despite normal Pald levels. This adaptation may be mediated by renal 11β-HSD2 activity, which, when normalized for GFR, became similar to that of control rats, suggesting that mineralocorticoid receptors maintain their aldosterone selectivity.


Documento: Artículo
Título:Role of 11β-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure
Autor:Yeyati, N.L.; Altuna, M.E.; Damasco, M.C.; Mac Laughlin, M.A.
Filiación:Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, calle Paraguay, 2155, 6th, 1421 Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:11β-HSD2; 5/6 Nephrectomy; Aldosterone; Potassium excretion; 11beta hydroxysteroid dehydrogenase 2; aldosterone; creatinine; potassium; sodium; spironolactone; 11beta hydroxysteroid dehydrogenase 2; aldosterone; potassium; aldosterone blood level; animal experiment; article; chronic kidney failure; controlled study; creatinine blood level; enzyme activity; enzyme inactivation; glomerulus filtration rate; hormone action; kidney microsome; male; nephrectomy; nonhuman; potassium balance; potassium excretion; potassium urine level; protein function; rat; receptor affinity; sham procedure; sodium excretion; sodium urine level; systolic blood pressure; animal; blood; blood pressure; enzymology; homeostasis; metabolism; microsome; physiology; Wistar rat; Rattus; Rattus norvegicus; 11-beta-Hydroxysteroid Dehydrogenase Type 2; Aldosterone; Animals; Blood Pressure; Homeostasis; Kidney Failure, Chronic; Male; Microsomes; Nephrectomy; Potassium; Rats; Rats, Wistar
Página de inicio:52
Página de fin:56
Título revista:Brazilian Journal of Medical and Biological Research
Título revista abreviado:Braz. J. Med. Biol. Res.
CAS:aldosterone, 52-39-1, 6251-69-0; creatinine, 19230-81-0, 60-27-5; potassium, 7440-09-7; sodium, 7440-23-5; spironolactone, 52-01-7; 11-beta-Hydroxysteroid Dehydrogenase Type 2,; Aldosterone, 52-39-1; Potassium, 7440-09-7


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---------- APA ----------
Yeyati, N.L., Altuna, M.E., Damasco, M.C. & Mac Laughlin, M.A. (2010) . Role of 11β-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure. Brazilian Journal of Medical and Biological Research, 43(1), 52-56.
Recuperado de [ ]
---------- CHICAGO ----------
Yeyati, N.L., Altuna, M.E., Damasco, M.C., Mac Laughlin, M.A. "Role of 11β-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure" . Brazilian Journal of Medical and Biological Research 43, no. 1 (2010) : 52-56.
Recuperado de [ ]
---------- MLA ----------
Yeyati, N.L., Altuna, M.E., Damasco, M.C., Mac Laughlin, M.A. "Role of 11β-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure" . Brazilian Journal of Medical and Biological Research, vol. 43, no. 1, 2010, pp. 52-56.
Recuperado de [ ]
---------- VANCOUVER ----------
Yeyati, N.L., Altuna, M.E., Damasco, M.C., Mac Laughlin, M.A. Role of 11β-hydroxysteroid dehydrogenase 2 renal activity in potassium homeostasis in rats with chronic renal failure. Braz. J. Med. Biol. Res. 2010;43(1):52-56.
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