Losartan prevented and regressed cardiac hypertrophy in stroke-prone spontaneously hypertensive rats, accompanied by reduced JNK and AP-1 activity, whereas hydralazine did not.
Does AT1 receptor antagonism with losartan prevent cardiac hypertrophy and reduce JNK activity in hypertensive rats?
AT1 receptor antagonism with losartan prevents and regresses cardiac hypertrophy in hypertensive rats by reducing JNK and AP-1 activity, an effect independent of blood pressure lowering alone.
In vitro studies on the role of the mitogen-activated protein (MAP) kinase family (extracellular signal-regulated kinase ERK, c-Jun NH(2)-terminal kinase JNK, and p38) in cardiac hypertrophic response have produced confusing and contradictory results. We examined the in vivo role of the angiotensin II type 1 (AT(1)) receptor in cardiac MAP kinase activities during both the onset and development of cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHRSP). In both the acute and chronic phases of cardiac hypertrophy in SHRSP, cardiac JNK activities were significantly increased compared with those in normotensive rats, whereas there was no prominent increase in cardiac ERK or p38 activities in SHRSP. Losartan, an AT(1) receptor antagonist, prevented the onset of cardiac hypertrophy and regressed the progression of cardiac hypertrophy in SHRSP, being accompanied by the reduction of JNK activity and activator protein-1 (AP-1) activity in SHRSP. However, in spite of the normalization of blood pressure, hydralazine did not prevent or regress cardiac hypertrophy and did not decrease JNK or AP-1 activity in SHRSP. Inversely, hydralazine significantly increased the cardiac ERK activity in SHRSP by enhancing its phosphorylation. In conclusion, we have obtained the first evidence that the AT(1) receptor is involved in the enhanced cardiac JNK activity in both the onset and development of cardiac hypertrophy of hypertensive rats. We propose that JNK is involved in AT(1) receptor-mediated cardiac hypertrophy in vivo, in part mediated by the activation of AP-1.
Izumi et al. (Sun,) conducted a other in Cardiac hypertrophy in hypertension. Losartan vs. Hydralazine and normotensive rats was evaluated on Cardiac hypertrophy and MAP kinase (JNK, ERK, p38) activities. Losartan prevented and regressed cardiac hypertrophy in stroke-prone spontaneously hypertensive rats, accompanied by reduced JNK and AP-1 activity, whereas hydralazine did not.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: