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) i s thought to contribute to the development of cardiac hypertrophy via its g rowth factor properties. The activation of mitogen-activated protein kinase s (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 toad were associated with specific cardiac MAPK pathw ays 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 he art of normotensive and hypertensive transgenic mice with AngII-mediated ca rdiac hypertrophy, Secondly, we used physiological models of AngII-dependen t and AngII-independent renovascular hypertension to study the activation o f cardiac MAPK pathways during the development of hypertrophy, Results In normotensive transgenic animals with AngII-induced cardiac hyper trophy, p38 activation is associated with the development of hypertrophy wh ile ERK and JNK are modestly stimulated. In hypertensive transgenic mice, f urther activation of ERK and JNK is observed. Moreover, in the AngII-indepe ndent model of renovascular hypertension and cardiac hypertrophy, p38 is no t 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 associ ated with the direct effects of AngII on cardiac cells, whereas stimulation of ERK and JNK occurs in association with AngII-induced mechanical stress. I Hypertens 2000, 18:1307-1317 (C) Lippincott Williams & Wilkins.