Buscar en
Endocrinología y Nutrición
Toda la web
Inicio Endocrinología y Nutrición Especificidad de acción de la aldosterona e hipertensión arterial
Información de la revista
Vol. 50. Núm. 1.
Páginas 14-18 (Enero 2003)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 50. Núm. 1.
Páginas 14-18 (Enero 2003)
DOI: 10.1016/S1575-0922(03)74490-8
Acceso a texto completo
Especificidad de acción de la aldosterona e hipertensión arterial
Specificity of the action of aldosterone and arterial hypertension
Visitas
...
N. Saval, A. Botey, E. Poch
Autor para correspondencia
epoch@medicina.ub.es

Correspondencia: Dr. E. Poch. Servicio de Nefrología. Hospital Clínic. Villarroel, 170. 08036 Barcelona. España
Servicio de Nefrología. Hospital Clínic. IDIBAPS. Barcelona. España
Información del artículo
Abstract

La enzima 11 beta-hidroxiesteroide deshidrogenasa tipo 2 (11βHSD2) confiere la especificidad de la acción de la aldosterona respecto a otros corticoides circulantes (cortisol) en los tejidos que deben responder de forma específica a los mineralocorticoides. Esta especificidad debe darse sobre todo en ciertos epitelios transportadores de sodio como el túbulo distal del riñón y en el colon. Esta enzima, poco conocida hasta hace unos años, se está revelando como de gran importancia, ya que interviene en la regulación de la presión arterial. En primer lugar, mutaciones del gen que codifica la enzima causan una forma rara de hipertensión sal sensible de herencia mendeliana autosómica recesiva conocida como exceso aparente de mineralocorticoides (AME). En segundo lugar, se ha determinado que en la población normal, polimorfismos genéticos en 11βHSD2 se asocian con una reducción de la actividad de la enzima in vivo. Esta reducción de la actividad enzimática así como los polimorfismos genéticos que la determinan se han relacionado con un incremento de la respuesta presora a la ingestión elevada de sal, fenómeno conocido como sensibilidad a la sal, tanto en sujetos sanos como en pacientes con hipertensión arterial esencial. Por tanto, es un gen candidato que intervendría en la patogenia de la hipertensión arterial (HTA) “gesencial”h, sobre todo sensible a la sal y que debe aún ser estudiado en mayor profundidad.

Palabras clave:
Aldosterona
Hipertensión
HSD11K
Túbulo renal distal
Abstract

The specificity of aldosterone with respect to other circulating corticoids (i.e. cortisol) in tissues which have to respond only to mineralocorticoids is provided by the enzime 11 beta hydroxysteroid dehydrogenase type 2 (11βHSD2). This specificity is especially criticval in certain Na-transporting epithelia such as the renal distal convoluted tubule and the distal colon. This enzime is emerging as a critical regulator of systemic blood pressure. Firstly, mutations in the gene encoding for this enzime are the cause of a rare autosomal recessive salt sensitive hypertension known as the apparent mineralocorticoid excess (AME).

Abstract

Secondly, common polymorphisms in this gene in the general population have been shown to influence the activity of the enzyme. Polymorphisms determining low enzymatic activity have been associated with increased pressor response to salt, a phenomenon known as salt-sentitivity, both in normal and in hypertensive subjects. Therefore, the gen encoding for 11βHSD2 is a candidate gene for essential hypertension, particularly the low-renin, salt sensitive form and deserves further study in hypertensive populations.

Key words:
Aldosterone
Hipertension
HSD11K
Distal convoluted tubule
El Texto completo está disponible en PDF
Bibliografía
[1.]
P.J. Fuller, S.S. Lim-Tio, F.E. Brenan.
Specificity in mineralcorticoid versus glucocorticoid action.
Kidney Int, 57 (2000), pp. 1256-1264
[2.]
N. Farman, B. Bocchi.
Mineralcorticoid selectivity: molecular and cellular aspects.
Kidney Int, 57 (2000), pp. 1364-1369
[3.]
J.L. Arriza, C. Weinberger.
Cloning human mineralcorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor.
Science, 273 (1987), pp. 268-275
[4.]
O. Melander.
Genetic factors in hypertension-What is known and what does it mean?.
Blood Press, 10 (2001), pp. 254-270
[5.]
P. Ferrari, Z. Krozowsky.
Role of 11b-hydroxysteroid dehydrogenase type 2 in blood presure regulation.
Kidney Int, 57 (2000), pp. 1374-1381
[6.]
A.L. Albiston, V.R. Obeyesekere, R.E. Smith, Z.S. Krozowski.
Cloning and tissue distribution of the human 11βÀ-hydroxysteroid dehydrogenase type 2 enzyme.
Mol Cell Endocrinol, 105 (2000), pp. R11-R17
[7.]
M. Lombes, S. Kenouch.
The mineralcorticoid receptor discriminates aldosterone from mineralcorticoids independently of the 11 beta-hydroxysteroid dehydrogenase.
Endocrinology, 135 (1994), pp. 834-840
[8.]
R.C. Wilson, S. Dave-Sharma, J.Q. Wei, V.R. Obeyesekere, K. Li, P. Ferrari, et al.
A genetic defect resulting in mild low-renin hypertension.
Proc Natl Acad Sci USA, 95 (1998), pp. 10200-10205
[9.]
D.J. Morris, Y.H. Lo, W. Reid Lichtfield, G.H. Williams.
Impact of dietary Na+ on Glycyrrhetinic Acid-Like Factors in human essential hypertension.
Hypertension, 31 (1998), pp. 469-472
[10.]
P. Ferrari, A. Sansonnens, B. Dick.
Frey FJ: In Vivo 11 (hydroxysteroid activity; Variability, salt-sensivity, and effect of licorice.
Hypertension, 38 (2000), pp. 1330-1336
[11.]
R. Alzamora, L. Michea, E.T. Marusic.
Role of 11βÀ-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries.
Hypertension, 35 (2000), pp. 1099-1104
[12.]
K.J. Biller, R.J. Unwin, D.G. Shirley.
Distal tubular electrolyte transport during inhibition of renal 11βÀ-hydroxisteroid dehydrogenase.
Am J Physiol Renal Physiol, 280 (2001), pp. F172-F179
[13.]
T. Mune, F.M. Rogerson, H. Nikkila, A.K. Agarwal, P.C. White.
Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase.
Nat Genet, 10 (1995), pp. 394-399
[14.]
P.C. White.
Inherited forms of mineralocorticoid hypertension.
Hypertension, 28 (1996), pp. 927-936
[15.]
A.K. Agarwal, F.M. Rogerson, T. Mune, P.C. White.
Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of the 11βÀ-hydroxisteroid dehydrogenase.
Genomics, 29 (1995), pp. 195-199
[16.]
Y. Kotelevtsev, R.W. Brown, S. Fleming, C. Kenyon, C. Edwuards, J. Seckl, et al.
Hypertension in mice lacking 11βÀ-hydroxysteroid dehydrogenase type 2.
J Clin Invest, 103 (1999), pp. 683-689
[17.]
B.S. Nunez, F.M. Rogerson, T. Mune, Y. Igarashi, Y. Nakagawa, G. Phillipov, et al.
Mutants of 11b-hydroxisteroid dehydrogenase with partial activity.
Hypertension, 34 (1999), pp. 638-642
[18.]
B. Watson, S.M. Bergman, A. Myracle, D.F. Callen, R.T. Acton, D.G. Warnock.
Genetic association of HSD11B2 flanking microsatellites with essential hypertension in blacks.
Hypertension, 28 (1996), pp. 478-482
[19.]
P.C. White, A.K. Agarwal, A. Li, H. Nikkila, J.H. Pratt, M. Caulfield, et al.
Possible association but no linkage of the HSD1B2 gene encoding the kidney isozyme of 11βÀ-hydroxisteroid dehydrogenase to hypertension in black people.
Clin Endocrinol, 55 (2001), pp. 249-252
[20.]
E. Brand, N. Kato, N. Chatelain, Z.S. Krozowski, X. Jeunemaitre, P. Corvol, et al.
Structural analysis and evaluation of the 11bhydroxisteroid dehydrogenase type 2 gene in human essential hypertension.
J Hypertens, 16 (1998), pp. 1627-1633
[21.]
A.C. Guyton, J.E. Hall, T.G. Coleman, R.D. Manning Jr., R.A. Norman Jr..
The dominant role of the kidney in long-term arterial pressure regulation in normal and hypertensive states.
Hypertension: Pathophysiology, diagnosis and management 2 nd e.d, pp. 1311-1326
[22.]
P.C. White, A.K. Agarwal, B.S. Nunez, G. Giacchetti, F. Mantero, P.M. Steward.
Genotype-phenotype correlations of mutations in the HSD11B2, the gene encoding the kidney isozyme of 11bhydroxisteroid dehidrogenase.
Endocrine Research, 2 (2000), pp. 771-780
[23.]
W.R. Litchfield, S.C. Hunt, X. Jeunemaitre, N.D.L. Fisher, P.N. Hopkins, R.R. Williams, et al.
Increased urinary free cortisol, a potential intermediate phenotype of essential hypertension.
Hypertension, 31 (1998), pp. 569-574
[24.]
E. Lovati, P. Ferrari, B. Dick, K. Jostarndt, B.M. Frey, F.J. Frey, et al.
Molecular basis of human salt sensivity: The role of the 11βÀ-hydroxisteroid dehydrogenase type 2.
J Clin Endocrinol Metab, 84 (1999), pp. 3745-3749
[25.]
A.K. Agarwal, G. Giacchetti, G. Lavery, H. Nikkila, M. Palermo, M. Ricketts, et al.
CA-repeat polymorphism in intron 1 of HSD11B2; effects on gene expression an salt sensivity.
Hypertension, 36 (2000), pp. 187-194
[26.]
Z. Smolenicka, E. Bach, A. Schaer, S. Liechti-Gallati, B.M. Frey, F.J. Frey, et al.
A new polymorphic site in human 11βÀ-hydroxisteroid dehydrogenase type 2 gene.
J Clin Endocrinol Metab, 83 (1998), pp. 1814-1817
[27.]
E. Poch, D. Gonzalez, V. Giner, E. Bragulat, A. Coca, A. De la Sierra.
Molecular basis of salt sensivity in human hypertension; evaluation of renin-angiotensin-aldosterone system gene polymorphisms.
Hypertension, 38 (2001), pp. 1204-1209
[28.]
J.R. Seckl, R. Benediktsson, S. Lindsay, R.W. Brown.
Placental 11βÀ-hidroxysteroid dehydrogenase and the programming of hypertension.
J Steroid Biochem Mol Biol, 55 (1995), pp. 447-455
Copyright © 2003. Elsevier España, S.L.. Todos los derechos reservados
Opciones de artículo
Herramientas
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.