Signaling pathways activated by vasoactive peptides in the cardiac myocyte and their role in myocardial pathologies.

In addition to its vasoactive effects, endothelin-1 (ET-1) causes hypertrophy of isolated cardiac myocytes. Since the early 1990s, the cell signaling events initiated by the binding of ET-1 to its cell surface receptors on the myocyte, and their roles in myocyte hypertrophy have been a particular interest of mine. ET-1 activates several intracellular signaling pathways in cardiac myocytes, notably the protein kinase C pathway and the mitogen-activated protein kinase cascades. It is likely that activation of these pathways contributes to the hypertrophic response. More recently, ET-1 has been shown to activate the phosphatidylinositol 3-kinase/Akt pathway, although the activation is relatively weak in comparison to other agonists. The actions of 2 other vasoactive peptides, angiotensin II and bradykinin, on the heart or cardiac myocyte in relation to cardiac hypertrophy are also discussed.