CYTOSOLIC CALCIUM CHANGES INDUCED BY ANGIOTENSIN-II IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS ARE MEDIATED VIA ANGIOTENSIN-II SUBTYPE-1 RECEPTORS

Objective To determine the effects of angiotensin II (AII) (1-8) on cy tosolic free calcium concentrations in the absence and in the presence of the selective angiotensin subtype 1 (AT(1)) receptor antagonist lo sartan and of the selective angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood mononuclear cells (PBMC), We also asse ssed the effect of the AII analogues AII (2-8), AII (3-8) and AII (4-8 ) on the cytosolic free-calcium concentration in human PBMC. Methods T he cytosolic free-calcium concentration was assayed in human periphera l blood mononuclear cells by measuring the fluorescence of fura-2 entr apped by these cells. Results Administration of AII caused a concentra tion-dependent increase in the cytosolic free-calcium concentration in human peripheral blood mononuclear cells with a half-maximal increase at 5 x 10(-8) mol/l, Also administration of the heptapeptide AII (2-8 ) increased the intracellular free-calcium concentration in human PBMC , whereas AII (3-8) and AII (4-8) had no effect, The AII (1-8)-induced rise in cytosolic free-calcium concentration was blocked completely b y losartan but not by P-186. Conclusion Our data demonstrate that the effects of AII on the cytosolic free-calcium concentration in human PB MC are AT(1) receptor-mediated since they were abolished by the specif ic AII AT(1) receptor antagonist losartan but not by the specific angi otensin subtype 2 receptor antagonist P-186.