Ras GTPases function as transducers of extracellular signals regulating many cell functions, and they appear to be involved in the development of hypertension. In the present study, we have investigated whether antihypertensive treatment with ARBs (angiotensin II receptor blockers), ACEi (angiotensin-converting enzyme inhibitors) and diuretics induce changes in Ras activation and in some of its effectors [ERK (extracellular-signal-regulated kinase) and Akt] in lymphocytes from patients with hypertension without or with diabetes. ACEi treatment transiently reduced Ras activation in the first month of treatment, but diuretics induced a sustained increase in Ras activation throughout the 3 months of the study. In patients with hypertension and diabetes, ARB, ACEi and diuretic treatment increased Ras activation only during the first week. ACEi treatment increased phospho-ERK expression during the first week and also in the last 2 months of the study; however, diuretic treatment reduced phospho-ERK expression during the last 2 months of the study. In patients with hypertension and diabetes, antihypertensive treatments did not induce changes in phospho-ERK expression in lymphocytes. ACEi treatment reduced phospho-Akt expression in patients with hypertension and diabetes only in the first month of treatment. In conclusion, these findings show that antihypertensive treatments with ACEi, and diuretics to a lesser extent, modify Ras activation and some of its signalling pathways, although in different directions, whereas ARBs do not appear to have any influence on Ras signalling pathways.
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Research Article|
December 15 2008
Effect of different antihypertensive treatments on Ras, MAPK and Akt activation in hypertension and diabetes
Lucas Fernández-Campo;
Lucas Fernández-Campo
*Centro de Salud de Matilla de los Caños, 37450 Salamanca, Spain
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María T. Grande;
María T. Grande
†Unidad de Fisiopatología Renal y Cardiovascular, Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain
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Julia Diego;
Julia Diego
‡Servicio de Nefrología, Hospital Virgen de la Concha, Zamora, Spain
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Isabel Fuentes-Calvo;
Isabel Fuentes-Calvo
†Unidad de Fisiopatología Renal y Cardiovascular, Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain
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Juan F. Macías-Núñez;
Juan F. Macías-Núñez
§Unidad de Hipertensión, Hospital Universitario de Salamanca, 37007 Salamanca, Spain
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Angel Sánchez-Rodríguez;
Angel Sánchez-Rodríguez
§Unidad de Hipertensión, Hospital Universitario de Salamanca, 37007 Salamanca, Spain
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Jesús Grande;
Jesús Grande
‡Servicio de Nefrología, Hospital Virgen de la Concha, Zamora, Spain
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Luis García-Ortiz;
Luis García-Ortiz
∥Unidad de Investigación, Centro de Salud de La Alamedilla, 37007 Salamanca, Spain
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José M. López-Novoa;
José M. López-Novoa
†Unidad de Fisiopatología Renal y Cardiovascular, Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain
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Carlos Martínez-Salgado
†Unidad de Fisiopatología Renal y Cardiovascular, Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain
¶Unidad de Investigación, Hospital Universitario de Salamanca, 37007 Salamanca, Spain
Correspondence: Dr Carlos Martínez-Salgado (email [email protected]).
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Publisher: Portland Press Ltd
Received:
April 09 2008
Revision Received:
June 05 2008
Accepted:
June 30 2008
Accepted Manuscript online:
June 30 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (2): 165–173.
Article history
Received:
April 09 2008
Revision Received:
June 05 2008
Accepted:
June 30 2008
Accepted Manuscript online:
June 30 2008
Citation
Lucas Fernández-Campo, María T. Grande, Julia Diego, Isabel Fuentes-Calvo, Juan F. Macías-Núñez, Angel Sánchez-Rodríguez, Jesús Grande, Luis García-Ortiz, José M. López-Novoa, Carlos Martínez-Salgado; Effect of different antihypertensive treatments on Ras, MAPK and Akt activation in hypertension and diabetes. Clin Sci (Lond) 1 January 2009; 116 (2): 165–173. doi: https://doi.org/10.1042/CS20080119
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