ANG II has been implicated in the hypertrophic response in ventricular myocytes by acting at the angiotensin type 1 (AT₁) receptor. However, the role of the angiotensin type 2 (AT₂) receptor in the adult heart is not as clearly understood. In adult rat ventricular myocytes (ARVM) and cardiac microvascular endothelial cells (CMEC), we examined the role of ANG II signaling, via AT₁ and AT₂ receptors, on the activation of the extracellular signal-regulated protein kinases (ERKs) and on the expression of the mitogen-activated protein kinase (MAPK) phosphatase MKP-1. ANG II caused no detectable increase in ERK activity or in c-fos mRNA abundance in ARVM but increased ERK activity within 5 min in CMEC and increased c-fos mRNA levels. However, in the presence of the selective phosphoprotein phosphatase (PP-2A/PP-1) inhibitor okadaic acid (OA), a sustained increase in ERK activity, as well as in c-jun NH₂-terminal protein kinase activity, in ARVM was observed. ANG II increased MKP-1 mRNA levels within 15 min in ARVM and CMEC. In contrast to the response in endothelial cells, however, ANG II activation of MKP-1 in ARVM was mediated by AT₂-receptor activation. Thus there is constitutive as well as inducible suppression of ERKs and c-jun NH₂-terminal protein kinases by MKP and PP-2A/PP-1 in the adult cardiac myocyte phenotype.