Hypertension Rapid Communication Angiotensin Increases Inositol Trisphosphate and Calcium in Vascular Smooth Muscle

Angiotensin II stimulated the breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and the generation of inositol trisphosphate (IP,) in cultured rat aortic smooth muscle cells. The decrease in PIP2 and increase in IP, levels were rapid (measurable at 5 seconds; maximum IP, levels at 15 seconds). The time course of these changes was comparable to that of angiotensin Il-induced increases in cytosolic free calcium, as measured by the calcium-sensitive fluorescent indicator quin 2. The IP3 formation was not stimulated by the calcium ionophore A23187 (5 /xM), nor were angiotensin Il-induced changes in IP, formation inhibited by the removal of extracellular calcium with EGTA. Angiotensin II appears to be capable of generating more IP, than is required for maximal release of intracellular calcium. These data are consistent with the hypothesis that generation of IP3 plays a role in the angiotensin Il-induced mobilization of calcium from intracellular storage sites in vascular smooth muscle cells. (Hypertension 7: 447-451, 1985)