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Clinical Science (2008) Immediate Publication, doi:10.1042/CS20080119
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Effect of different antihypertensive treatments on Ras / MAPKinases / Akt activation in hypertension and diabetes
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Lucas Fernández-Campo, María T. Grande, Julia Diego, Isabel Fuentes-Calvo, Juan Florencio Macías-Núñez, Angel Sánchez-Rodríguez, Jesús Grande, Luis García-Ortiz, Jose M. López-Novoa and Carlos Martínez-Salgado
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Unidad de Investigacion, Sacyl-Hospital Universitario de Salamanca, Salamanca 37007, Spain. carlosms@usal.es
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Ras GTPases function as transducers of extracellular signals regulating many cell functions, and they seem to be involved in the development of hypertension. We have evaluated whether the antihypertensive treatment with angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACEi), and diuretics induce changes in Ras activation and in some of its effectors (Erk and Akt) in lymphocytes from hypertensive and diabetic patients.
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 diabetic-hypertensive patients, ARB, ACEi and diuretics 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 diabetic-hypertensive patients, antihypertensive treatments did not induce changes on phospho-Erk expression in lymphocytes. ACEi treatment reduced phospho-Akt expression in diabetic patients only in the first month of treatment.
These data show that antihypertensive therapies with ACEi, and diuretics to a lesser extent, modify Ras activation and some of its signalling pathways, even though in different directions; ARB do not seem to have any influence on Ras signalling pathways.
doi:10.1042/CS20080119
Received 9 April 2008/5 June 2008; Accepted 30 June 2008
Published as Immediate Publication 30 June 2008
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