Angiotensin II stimulates hypertrophic growth of cultured neonatal rat ventricular myocytes: roles of PKC and PGF2alpha

Angiotensin II (Ang II) has been shown to regulate growth in smooth muscle cells. Protein kinase C (PKC), which mediates Ang II action, has been impli cated in myocardial cell hypertrophy. Acute pressure overload in the left v entricles has been demonstrated to produce prostaglandin F2 alpha (PGF2alph a) release. Therefore, we used cultured neonatal rat ventricular myocytes t o study Ang II, PKC and PGF2alpha and their relationship to hypertrophy. Th e amount of PGF2alpha produced was determined by radioimmunoassay, Ang It-i nduced hypertrophy and PGF2alpha release. Pretreatment with 10-6M of PKC in hibitor, 1-(5-isoquinolinesulfonyl-methyl) piperazine (H7), blocked Ang II- induced hypertrophy and PGF2alpha release. In neonatal rat ventricular myoc ytes that were treated with either Ang II or PKC activator (Phorbol 12, 13, dibutyrate; PDBu), PKC enzyme assay showed PKC was translocated from the c ytosol to the membrane which indicates activation. This suggests that PKC m ediates, in part, Ang II-induced PGF2alpha release and hypertrophy. In summ ary, Ang II activates PKC, which causes PGF2alpha release and hypertrophy, and this PGF2alpha release and hypertrophy can be overcome by pretreatment with PKC inhibitor (C) 2000 Harcourt Publishers Ltd.