ROLE OF AT(1) AND AT(2) RECEPTORS IN REGULATION OF MAPKS AND MKP-1 BYANG-II IN ADULT CARDIAC MYOCYTES

ANG II has been implicated in the hypertrophic response in ventricular myocytes by acting at the angiotensin type 1 (AT(1)) receptor However , the role of the angiotensin type 2 (AT(2)) receptor in the adult hea rt is not as clearly understood. In adult rat ventricular myocytes (AR VM) and cardiac microvascular endothelial cells (CMEC), we examined th e role of ANG II signaling, via AT(1) and AT(2) receptors, on the acti vation of the extracellular signal-regulated protein kinases (ERKs) an d on the expression of the mitogen-activated protein kinase (MAPK) pho sphatase MKP-1. ANG II caused no detectable increase in ERK activity o r 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 oka daic 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 contra st to the response in endothelial cells, however, ANG II activation of MKP-1 in ARVM was mediated by AT(2)-receptor activation. Thus there i s 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 my ocyte phenotype.