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Effect of different antihypertensive treatments on Ras, MAPK and Akt activation in hypertension and diabetes.

Authors
  • Fernández-Campo, Lucas
  • Grande, María T
  • Diego, Julia
  • Fuentes-Calvo, Isabel
  • Macías-Núñez, Juan F
  • Sánchez-Rodríguez, Angel
  • Grande, Jesús
  • García-Ortiz, Luis
  • López-Novoa, José M
  • Martínez-Salgado, Carlos
Type
Published Article
Journal
Clinical Science
Publisher
Portland Press
Publication Date
Jan 01, 2009
Volume
116
Issue
2
Pages
165–173
Identifiers
DOI: 10.1042/CS20080119
PMID: 18588512
Source
Medline
License
Unknown

Abstract

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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