title: Endothelium-derived bradykinin is responsible for the increase in calcium produced by angiotensin-converting enzyme inhibitors in human endothelial cells.
abstract: The effects of angiotensin-converting enzyme (ACE) inhibitors on intracellular calcium concentration ([Ca2+]i) were examined under resting conditions and after stimulation with bradykinin in cultured human umbilical vein endothelial cells. The ACE inhibitors ramiprilat and enalaprilat (0.3 microM) enhanced the increase in [Ca2+]i elicited by bradykinin (3 nM) and also caused an increase in resting [Ca2+]i when given alone. This increase in resting [Ca2+]i was long-lasting and accompanied by an increased formation of nitric oxide, as assessed by a NG-nitro-L-arginine-sensitive cyclic GMP accumulation in the cells. Both increases in resting [Ca2+]i and nitric oxide production by ACE inhibitors were inhibited by preincubation of the cells with the B2-receptor antagonist Hoe 140. These data indicate that ACE inhibitors are able to unmask a release of bradykinin from cultured human endothelial cells. This endothelium-derived bradykinin can exert an autocrine function by stimulating endothelial B2-receptors with a subsequent increase in [Ca2+]i and nitric oxide formation.
authors.affiliation: Institut für Angewandte Physiologie, Universität Freiburg, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Busse
authors.forename: D
authors.initials: D
authors.lastname: Lamontagne
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D000242:Cyclic AMP; D001920:Bradykinin; D002118:Calcium