The effect of angiotensin II on mitogen-activated protein kinase in human cardiomyocytes

• DOI: 10.3317/jraas.2000.070
• Publication Date: 2007-05-25T08:52:19Z
• Authors: Chiming Wei; Marcelo G Cardarelli; Stephen W Downing; Joseph S McLaughlin
• Keywords: 0303 health sciences; Pyridines; Angiotensin II; Myocardium; Imidazoles; JNK Mitogen-Activated Protein Kinases; Drug Synergism; Middle Aged; Receptor, Angiotensin, Type 2; p38 Mitogen-Activated Protein Kinases; Losartan; Receptor, Angiotensin, Type 1; 3. Good health; Enzyme Activation; Angiotensin Receptor Antagonists; 03 medical and health sciences; Culture Techniques; Humans; Mitogen-Activated Protein Kinases; Aged

The role of angiotensin II (Ang II)-receptors on mitogen-activated protein kinase (MAPK) activation in cardiomyocytes remains controversial. Therefore, the current study was designed to investigate the actions of AT1- and AT2-receptors on Ang II-induced extracellular signal-regulated kinase (ERK), p38 and the c-Jun N-terminal kinase (JNK) MAPK activities in human cardiomyocytes. Human cardiac tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced and incubated in the special tissue culture system for 24 hours in the absence or presence of Ang II (10-7 M). These studies were repeated with the AT1-receptor antagonist losartan (10-6 M) or the AT2-receptor antagonist PD-123319 (10-6 M). Immunohistochemical staining and Western blot analysis with phospho-antibodies were performed to determine ERK, JNK and p38 activities. Ang II increased ERK and p38 activities in human cardiomyocytes. The effects of Ang II were abolished by losartan and enhanced by PD-123319. Co-incubation with both losartan and PD-123319 resulted in a decrease of ERK and p38 activities in cardiomyocytes. The immunohistochemical staining of JNK showed no significant differences between Ang II alone, Ang II plus losartan and Ang II plus PD-123319 groups. In conclusion, Ang II has a potent effect on ERK and p38 MAPK activities in cardiomyocytes, by acting through AT1-receptors. This effect of Ang II is modified by AT2-receptors. Therefore, Ang II, via AT1- and AT2-receptor stimulation, has a distinct effect on MAPK activity in cardiomyocytes.