Angiotensin II Stimulation of Vascular Smooth Muscle

Abstract

Angiotensin II (Ang II) stimulation of vascular smooth muscle results in a myriad of intracellular signals that interact to produce the final physiologic response of the cell. One of the earliest documented events following incubation of these cells with Ang II is the rapid, phospholipase C-mediated hydrolysis of phosphatidylinositol-4,5-bisphosphate to yield two second messengers, inositol trisphosphate and diacylglycerol. Inositol trisphosphate releases calcium from nonmitochondrial intracellular storage sites, while diacylglycerol activates protein kinase C. Ang II also stimulates calcium influx and increases calcium efflux for the duration of the stimulus, as well as causing a biphasic change in intracellular pH. The delayed alkalinization is a consequence of enhanced Na+/H+ exchange. These signals then interact to modify the targets of phospholipase C, and result in phosphorylation of numerous cytoplasmic and cytoskeletal proteins. Thus, the signaling events induced by Ang II are complex, and dynamically interact to produce a constantly changing response for the duration of the stimulus.