REGULATION OF CYTOSOLIC CALCIUM BY ANGIOTENSINS IN VASCULAR SMOOTH-MUSCLE

The carboxy terminal homologue of angiotensin ? (Aug II), Ang-(3-8) or hexa peptide, was used as a model peptide to examine the types of receptor mechanisms involved in calcium mobilization in cultured vascular smooth muscle cells. Hexapepdde did not produce tachyphylaxis but did produce a sustained increase in intracellular calcium. Differences in the increase in intracellular calcium ([Ca2+]1) and the pattern of inositol phosphate production indicate that Ang-(3-8) and maxima] concentrations of Ang II mobilize calcium through different mechanisms. The calcium-mobilizing mechanisms that predominate appear to depend on the concentration of angiotensin. Concentrations of Ang II greater than I0-8M produce sharp calcium transients in which the [Ca2+]1 returns close to baseline within 1 minute after stimulation, but concentrations of Ang II equal to or less than 3x10-9 M result in a plateau increase in calcium. Pretreatment with Bordetella pertussis toxin does not abolish either the calcium transient induced by Ang II or the plateau phase induced by Ang-(3-8), indicating that the GTP-transducing protein that couples the receptor to phospholipase C or, possibly, a receptor-operated calcium channel is not Bordetella pertussis toxin sensitive. © 1990 American Heart Association, Inc.