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Abstract:

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.

Registro:

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
Año:2010
Volumen:43
Número:1
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.
ISSN:0100879X
CODEN:RBPMB
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, 1.1.1.146; Aldosterone, 52-39-1; Potassium, 7440-09-7
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0100879X_v43_n1_p52_Yeyati

Referencias:

  • Gennari, F.J., Segal, A.S., Hyperkalemia: An adaptive response in chronic renal insufficiency (2002) Kidney Int, 62, pp. 1-9
  • Musso, C.G., Miguel, R., Algranati, L., Farias, E.R., Renal potassium excretion: Comparison between chronic renal disease patients and old people (2005) Int Urol Nephrol, 37, pp. 167-170
  • Bourgoignie, J.J., Gavellas, G., Van Putten, V., Berl, T., Potassium-aldosterone response in dogs with chronic renal insufficiency (1985) Miner Electrolyte Metab, 11, pp. 150-154
  • Musso, C.G., Potassium metabolism in patients with chronic kidney disease (CKD), Part I: Patients not on dialysis (stages 3-4) (2004) Int Urol Nephrol, 36, pp. 465-468
  • Hene, R.J., Boer, P., Koomans, H.A., Mees, E.J., Plasma aldosterone concentrations in chronic renal disease (1982) Kidney Int, 21, pp. 98-101
  • Navaneethan, S.D., Nigwekar, S.U., Sehgal, A.R., Strippoli, G.F., Aldosterone antagonists for preventing the progression of chronic kidney disease (2009) Cochrane Database Syst Rev, , CD007004
  • Hene, R.J., Koomans, H.A., Boer, P., Dorhout Mees, E.J., Effect of high-dose aldosterone infusions on renal electrolyte excretion in patients with renal insufficiency (1987) Am J Nephrol, 7, pp. 33-37
  • Berl, T., Katz, F.H., Henrich, W.L., de Torrente, A., Schrier, R.W., Role of aldosterone in the control of sodium excretion in patients with advanced chronic renal failure (1978) Kidney Int, 14, pp. 228-235
  • Todd-Turla, K.M., Schnermann, J., Fejes-Toth, G., Naray-Fejes-Toth, A., Smart, A., Killen, P.D., Distribution of mineralocorticoid and glucocorticoid receptor mRNA along the nephron (1993) Am J Physiol, 264, pp. F781-F791
  • Arriza, J.L., Weinberger, C., Cerelli, G., Glaser, T.M., Handelin, B.L., Housman, D.E., Cloning of human mineralocorticoid receptor complementary DNA: Structural and functional kinship with the glucocorticoid receptor (1987) Science, 237, pp. 268-275
  • Escher, G., Frey, B.M., Frey, F.J., 11 beta-hydroxysteroid dehydrogenase - why is it important for the nephrologist? (1995) Nephrol Dial Transplant, 10, pp. 1506-1509
  • Funder, J.W., Pearce, P.T., Smith, R., Smith, A.I., Mineralocorticoid action: Target tissue specificity is enzyme, not receptor, mediated (1988) Science, 242, pp. 583-585
  • Zallocchi, M.L., Matkovic, L., Calvo, J.C., Damasco, M.C., Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2 (2004) J Cell Biochem, 92, pp. 591-602
  • Biller, K.J., Unwin, R.J., Shirley, D.G., Distal tubular electrolyte transport during inhibition of renal 11beta-hydroxysteroid dehydrogenase (2001) Am J Physiol Renal Physiol, 280, pp. F172-F179
  • Morris, D.J., Latif, S.A., Brem, A.S., Interactions of mineralocorgroups ticoids and glucocorticoids in epithelial target tissues revisited (2009) Steroids, 74, pp. 1-6
  • Vantyghem, M.C., Marcelli-Tourvieille, S., Defrance, F., Wemeau, J.L., 11beta-hydroxysteroid dehydrogenases. Recent advances] (2007) Ann Endocrinol, 68, pp. 349-356
  • Bonvalet, J.P., Doignon, I., Blot-Chabaud, M., Pradelles, P., Farman, N., Distribution of 11 beta-hydroxysteroid dehydrogenase along the rabbit nephron (1990) J Clin Invest, 86, pp. 832-837
  • Whorwood, C.B., Barber, P.C., Gregory, J., Sheppard, M.C., Stewart, P.M., 11 beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in the rat colon (1993) Am J Physiol, 264, pp. E951-E957
  • Heiniger, C.D., Kostadinova, R.M., Rochat, M.K., Serra, A., Ferrari, P., Dick, B., Hypoxia causes down-regulation of 11 beta-hydroxysteroid dehydrogenase type 2 by induction of Egr-1 (2003) FASEB J, 17, pp. 917-919
  • Quinkler, M., Zehnder, D., Lepenies, J., Petrelli, M.D., Moore, J.S., Hughes, S.V., Expression of renal 11beta-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function (2005) Eur J Endocrinol, 153, pp. 291-299
  • Bistrup, C., Thiesson, H.C., Jensen, B.L., Skott, O., Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats (2005) Acta Physiol Scand, 184, pp. 161-169
  • Morrison, A.B., Experimentally induced chronic renal insufficiency in the rat (1962) Lab Invest, 11, pp. 321-332
  • Ortiz, R.M., Graciano, M.L., Mullins, J.J., Mitchell, K.D., Aldosterone receptor antagonism alleviates proteinuria, but not malignant hypertension, in Cyp1a1-Ren2 transgenic rats (2007) Am J Physiol Renal Physiol, 293, pp. F1584-F1591
  • Juknevicius, I., Segal, Y., Kren, S., Lee, R., Hostetter, T.H., Effect of aldosterone on renal transforming growth factor-beta (2004) Am J Physiol Renal Physiol, 286, pp. F1059-F1062
  • Virdis, A., Neves, M.F., Amiri, F., Viel, E., Touyz, R.M., Schiffrin, E.L., Spironolactone improves angiotensin-induced vascular changes and oxidative stress (2002) Hypertension, 40, pp. 504-510
  • Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254
  • Igarreta, P., Calvo, J.C., Damasco, M.C., Activity of renal 11beta-hydroxysteroid dehydrogenase 2 (11betaHSD2) in stressed animals (1999) Life Sci, 64, pp. 2285-2290
  • Leenen, F.H., de Jong, W., A solid silver clip for induction of predictable levels of renal hypertension in the rat (1971) J Appl Physiol, 31, pp. 142-144
  • Slot, C., Plasma creatinine determination. A new and specific Jaffe reaction method (1965) Scand J Clin Lab Invest, 17, pp. 381-387
  • Van Liew, J.B., Zamlauski-Tucker, M.J., Feld, L.G., Endogenous creatinine clearance in the rat: Strain variation (1993) Life Sci, 53, pp. 1015-1021
  • Bricker, N.S., On the meaning of the intact nephron hypothesis (1969) Am J Med, 46, pp. 1-11
  • Meyer, T.W., Scholey, J.W., Brenner, B.M., Nephron adaptation to renal injury (1991) The kidney, pp. 1872-1890. , Brenner BM, Rector FC Editors, 4th edn. Philadelphia: W.B. Saunders;
  • Allison, M.E., Wilson, C.B., Gottschalk, C.W., Pathophysiology of experimental glomerulonephritis in rats (1974) J Clin Invest, 53, pp. 1402-1423
  • Kramp, R.A., MacDowell, M., Gottschalk, C.W., Oliver, J.R., A study by microdissection and micropuncture of the structure and the function of the kidneys and the nephrons of rats with chronic renal damage (1974) Kidney Int, 5, pp. 147-176
  • Levy, Y.N., Fellet, A., Arranz, C., Balaszczuk, A.M., Adrogue, H.J., Amiloride-sensitive and amiloride-insensitive kaliuresis in advanced chronic kidney disease (2008) J Nephrol, 21, pp. 93-98
  • Frassetto, L., Morris Jr, R.C., Sellmeyer, D.E., Todd, K., Sebastian, A., Diet, evolution and aging - the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet (2001) Eur J Nutr, 40, pp. 200-213
  • Malnic, G., Klose, R.M., Giebisch, G., Micropuncture study of renal potassium excretion in the rat (1964) Am J Physiol, 206, pp. 674-686
  • Audige, A., Dick, B., Frey, B.M., Frey, F.J., Corman, B., Vogt, B., Glucocorticoids and 11 beta-hydroxysteroid dehydrogenase type 2 gene expression in the aging kidney (2002) Eur J Clin Invest, 32, pp. 411-420
  • Dunnill, M.S., Halley, W., Some observations on the quantitative anatomy of the kidney (1973) J Pathol, 110, pp. 113-121
  • McLachlan, M.S., Guthrie, J.C., Anderson, C.K., Fulker, M.J., Vascular and glomerular changes in the ageing kidney (1977) J Pathol, 121, pp. 65-78

Citas:

---------- 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 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0100879X_v43_n1_p52_Yeyati [ ]
---------- 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 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0100879X_v43_n1_p52_Yeyati [ ]
---------- 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 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0100879X_v43_n1_p52_Yeyati [ ]
---------- 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.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0100879X_v43_n1_p52_Yeyati [ ]