Phosphoinositide Hydrolysis and Calcium Mobilization Induced by Vasopressin and Angiotensin II in Cultured Vascular Smooth Muscle Cells

The cellular action of vasoconstrictive hormones, angiotensin II (AII) and Arg⁸-vasopressin (AVP), on vascular smooth muscle (VSM) in cultured VSM cells from rat mesenteric artery was studied. Both AII and AVP specifically induce a transient increases in cytosolic free calcium independent of extracellular calcium or calcium channels activated by high potassium depolarization in VSM cells loaded with Fura-2. Vasoconstrictive hormones induce a dose-dependency with formation of inositolphosphates. Analysis using high pressure liquid chromatography has shown that AVP stimulates rapid and transient increases in inositol 1, 3, 4-trisphosphate, inositol 1, 4, 5-trisphosphate and inositol 1, 3, 4, 5-tetrakisphosphate within 1 minute. Moreover, a laser-excitation fluorescence system reveals high calcium concentration sites in subsarcolemmal region. These results indicate that, unlike voltage-dependent calcium influx across the cell membrane, AII and AVP induce receptor-mediated increases in cytosolic free calcium via phosphoinositide hydrolysis creating an intracellular messenger for calcium release from intracellular calcium stores.