Effect of different antihypertensive treatments on Ras, MAPK and Akt activation in hypertension and diabetes.
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.
Fernández-Campo
Lucas
L
Centro de Salud de Matilla de los Caños, 37450 Salamanca, Spain.
Grande
María T
MT
Diego
Julia
J
Fuentes-Calvo
Isabel
I
Macías-Núñez
Juan F
JF
Sánchez-Rodríguez
Angel
A
Grande
Jesús
J
García-Ortiz
Luis
L
López-Novoa
José M
JM
Martínez-Salgado
Carlos
C
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D004232:Diuretics / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000097:blood*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood*; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000097:blood*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins