ROLE OF CALCIUM IN ANGIOTENSIN-II-INDUCED PROSTAGLANDIN RELEASE AND DNA-SYNTHESIS IN RAT VASCULAR SMOOTH-MUSCLE CELLS

Cellular calcium modulates enzyme activity, cell proliferation, and di fferentiation. In vascular smooth muscle cells (VSMC), calcium may con tribute to increased vascular contractility and structural alterations in both hypertension and atherosclerosis. We investigated the role of calcium in angiotensin II (AII)-induced prostaglandin release and DNA synthesis in VSMC. Prostaglandin levels were determined by radioimmun oassay, and DNA synthesis was determined by the incorporation of [H-3] thymidine. AII dose-dependently stimulated the release of prostaglandi n E(2) and prostaglandin I-2, and this effect was synergistically enha nced by the Ca2+ ionophore A23187. Conversely, the AII response was in hibited by EGTA, a chelator of Ca2+ ions and by verapamil and nifedipi ne, two Ca2+ channel blockers or by incubation of the cells without ex ogenous Ca2+. TMB-8, an inhibitor of calcium mobilization, also strong ly reduced angiotensin response. Similar results were obtained far ang iotensin III (AIII) and vasopressin, two other agonists of prostagland in production. AII- or serum-stimulated DNA synthesis was almost aboli shed by EGTA, whereas TMB-8, verapamil, and nifedipine had little or n o effect. The production of prostaglandins triggered by angiotensins a nd vasopressin in VSMC is dependent on both intracellular and extracel lular calcium, with calcium entering through L-type Ca2+ channels. Ext racellular calcium is important for AII and serum mitogenic activity, but L-type Ca2+ channels do not appear to be implicated.