Angiotensin II rapidly increases phosphatidate-phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells.
Smooth muscle cells were cultured from rat thoracic aorta and labeled to a stable specific activity with 45Ca2+, myo-[2-3H]inositol, or 32Pi. The efflux of 45Ca2+ was monitored over 10-sec intervals. Angiotensin II (AII) increased the amount of 45Ca2+ lost by 5-fold in the first 10-sec interval after the addition of AII and by 10-fold in the second 10-sec interval. AII-stimulated 45Ca2+ release was blocked by the angiotensin antagonist [1-sarcosine, 8-leucine]AII and by La3+. The removal of external Ca2+ had no effect on AII-stimulated 45Ca2+ release. Depolarization with high external K+ only slightly increased 45Ca2+ efflux and had no effect on AII-induced 45Ca2+ release. AII had no effect on the initial rate of 45Ca2+ influx. These results indicate that the rapid 45Ca2+ efflux evoked by AII is probably due to the release of 45Ca2+ sequestered intracellularly rather than to an increase in the Ca2+ permeability of the plasma membrane. AII provoked rapid increases in the levels of phosphatidic acid and phosphoinositides in the cells. These increases in phospholipids were associated with increases in phospholipase C-generated inositol phosphates (tri-, di-, and mono-). It appears that AII simultaneously increases phosphoinositide hydrolysis and synthesis in vascular smooth muscle, and both phospholipid effects may contribute to inositol triphosphate generation, which was sufficiently rapid to have a role in intracellular Ca2+ mobilization.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006868:Hydrolysis; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D000804:Angiotensin II; D002118:Calcium