P Lijnen1, R Fagard, V Petrov. 1. Department of Molecular and Cardiovascular Research, Catholic University of Leuven, Belgium.
Abstract
OBJECTIVE: To determine the effects of angiotensin II (AII) (1-8) on cytosolic free calcium concentrations in the absence and in the presence of the selective angiotensin subtype 1 (AT1) receptor antagonist losartan and of the selective angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood mononuclear cells (PBMC). We also assessed 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: The cytosolic free-calcium concentration was assayed in human peripheral blood mononuclear cells by measuring the fluorescence of fura-2 entrapped by these cells. RESULTS: Administration of AII caused a concentration-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 by losartan but not by P-186. CONCLUSION: Our data demonstrate that the effects of AII on the cytosolic free-calcium concentration in human PBMC are AT1 receptor-mediated since they were abolished by the specific AII AT1 receptor antagonist losartan but not by the specific angiotensin subtype 2 receptor antagonist P-186.
OBJECTIVE: To determine the effects of angiotensin II (AII) (1-8) on cytosolic free calcium concentrations in the absence and in the presence of the selective angiotensin subtype 1 (AT1) receptor antagonist losartan and of the selective angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood mononuclear cells (PBMC). We also assessed 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: The cytosolic free-calcium concentration was assayed in human peripheral blood mononuclear cells by measuring the fluorescence of fura-2 entrapped by these cells. RESULTS: Administration of AII caused a concentration-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 by losartan but not by P-186. CONCLUSION: Our data demonstrate that the effects of AII on the cytosolic free-calcium concentration in human PBMC are AT1 receptor-mediated since they were abolished by the specific AIIAT1 receptor antagonist losartan but not by the specific angiotensin subtype 2 receptor antagonist P-186.
Authors: C Nataraj; M I Oliverio; R B Mannon; P J Mannon; L P Audoly; C S Amuchastegui; P Ruiz; O Smithies; T M Coffman Journal: J Clin Invest Date: 1999-12 Impact factor: 14.808