Angiotensin II-induced cardiac hypertrophy is associated with different mitogen-activated protein kinase activation in normotensive and hypertensive mice.
OBJECTIVE
In addition to its haemodynamic effects, angiotensin II (AngII) is thought to contribute to the development of cardiac hypertrophy via its growth factor properties. The activation of mitogen-activated protein kinases (MAPK) is crucial for stimulating cardiac growth. Therefore, the present study aimed to determine whether the trophic effects of AngII and the AngII-induced haemodynamic load were associated with specific cardiac MAPK pathways during the development of hypertrophy. Methods The activation of the extracellular-signal-regulated kinase (ERK), the c-jun N-terminal kinase (JNK) and the p38 kinase was followed in the heart of normotensive and hypertensive transgenic mice with AngII-mediated cardiac hypertrophy. Secondly, we used physiological models of AngII-dependent and AngII-independent renovascular hypertension to study the activation of cardiac MAPK pathways during the development of hypertrophy.


RESULTS
In normotensive transgenic animals with AngII-induced cardiac hypertrophy, p38 activation is associated with the development of hypertrophy while ERK and JNK are modestly stimulated. In hypertensive transgenic mice, further activation of ERK and JNK is observed. Moreover, in the AngII-independent model of renovascular hypertension and cardiac hypertrophy, p38 is not activated while ERK and JNK are strongly stimulated. In contrast, in the AngII-dependent model, all three kinases are stimulated.


CONCLUSIONS
These data suggest that p38 activation is preferentially associated with the direct effects of AngII on cardiac cells, whereas stimulation of ERK and JNK occurs in association with AngII-induced mechanical stress.
Pellieux
C
C
Division of Hypertension, University of Lausanne Medical School, Switzerland.
Sauthier
T
T
Aubert
J F
JF
Brunner
H R
HR
Pedrazzini
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D018995:Myosin Heavy Chains / Q000235:genetics; D011401:Promoter Regions, Genetic; D012083:Renin / Q000235:genetics; D013314:Stress, Mechanical; D019076:Transgenes / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D014662:Vasoconstrictor Agents; D000808:Angiotensinogen; D000804:Angiotensin II; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D012083:Renin; D018995:Myosin Heavy Chains