Angiotensin II stimulation of vascular smooth muscle phosphoinositide metabolism. State of the art lecture.

Phosphoinositide hydrolysis is an integral step in the activation of vascular smooth muscle by angiotensin II. Sequential phospholipase C-mediated hydrolysis of the polyphosphoinositides and phosphatidylinositol in cultured vascular smooth muscle cells stimulated with angiotensin II results in a coordinated series of biochemical events: a transient formation of inositol trisphosphate associated with calcium mobilization, and a biphasic, sustained formation of diacylglycerol associated with activation of protein kinase C and cytosolic alkalinization. The initial, rapid phase and the sustained phase of the angiotensin II response appear to be differentially controlled. Formation of inositol trisphosphate and mobilization of calcium are attenuated by activation of protein kinase C. Sustained diacylglycerol formation is promoted by cytosolic alkalinization, and appears to require cellular processing of the angiotensin II-receptor complex. Calcium and cyclic guanosine 3',5'-monophosphate do not appear to regulate phospholipase C-mediated phosphoinositide hydrolysis in vascular smooth muscle. Thus, regulation of angiotensin II-stimulated second messenger generation in vascular smooth muscle is complex, perhaps involving protein kinase C activation, changes in intracellular pH, and processing of the angiotensin II-receptor complex.