Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells

Until recently, the signaling events elicited in vascular smooth muscle cel ls by angiotensin II (Ang II) were considered to be rapid, short-lived, and divided into separate linear pathways, where intracellular targets of the phospholipase C-diacylglycerol-Ca (2+) axis were distinct from those of the tyrosine kinase- and mitogen-activated protein kinase- dependent pathways. However, these major intracellular signaling cascades do not function inde pendently and are actively engaged in cross-talk. Downstream signals from t he Ang II-bound receptors converge to elicit complex and multiple responses . The exact adapter proteins or "go-between" molecules that link the multip le intracellular pathways await clarification. Ang II induces a multitude o f actions in various tissues, and the signaling events following occupancy and activation of angiotensin receptors are tightly controlled and extremel y complex. Alterations of these highly regulated signaling pathways in vasc ular smooth cells may be pivotal in structural and functional abnormalities that underlie vascular pathological processes in cardiovascular diseases s uch as hypertension, atherosclerosis, and post-interventional restenosis.