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 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.


CONCLUSIONS
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.
Lijnen
P
P
Department of Molecular and Cardiovascular Research, Catholic University of Leuven, Belgium.
Fagard
R
R
Petrov
V
V
D000804:Angiotensin II / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*
D005456:Fluorescent Dyes; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C104454:angiotensin II (1-8); D000804:Angiotensin II; D002118:Calcium; D016257:Fura-2