Alterations of cardiac ERK1/2 expression and activity due to volume overload were attenuated by the blockade of RAS.
The activities and protein content of extracellular signal-regulated kinase (ERK)1/2 in the heart were measured in rats at 4 and 16 weeks after volume overload due to aortocaval shunt. Protein content of phosphorylated ERK1/2 was increased at both 4 and 16 weeks, whereas protein content of total ERK1/2 was increased only at 16 weeks of inducing volume overload. The ERK1/2 activities, estimated as phospho-Elk-1 content, were also increased at 4 and 16 weeks of inducing volume overload. The increased phosphorylated ERK1/2 and E-26-like (Elk)-1 protein content in 16 weeks failing hearts was much greater than that in 4 weeks hypertrophied hearts. These changes in phosphorylated ERK1/2 and Elk-1 protein content in both 4 and 16 weeks volume overloaded animals were attenuated by treatment with enalapril and/or losartan. The results indicate that activation of ERK1/2 may be involved in the development of cardiac hypertrophy and heart failure due to volume overload, and these changes are partially prevented by blockade of the renin-angiotensin system (RAS).
Zhang
Weihua
W
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Elimban
Vijayan
V
Xu
Yan Jun
YJ
Zhang
Ming
M
Nijjar
Mohinder S
MS
Dhalla
Naranjan S
NS
D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D006332:Cardiomegaly / Q000188:drug therapy / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics; D019808:Losartan / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019808:Losartan