title: Enhancement of cytosolic calcium, prostacyclin and nitric oxide by bradykinin and the ACE inhibitor ramiprilat in porcine brain capillary endothelial cells.
abstract: We studied whether primary cultured porcine brain capillary endothelial cells (PBCEC) respond to bradykinin with an enhanced intracellular cytosolic calcium concentration [Ca2+]i with subsequent formation of nitric oxide (NO) and prostacyclin (PGI2). In addition we examined whether these cells synthetize and release kinins that may accumulate during angiotensin-converting enzyme (ACE) inhibition. [Ca2+]i was assessed by the fluorescent dye Fura-2, NO formation by determination of intracellular cyclic GMP and PGI2 by a specific radioimmunoassay for 6-ketoprostaglandin F1 alpha. Bradykinin and the ACE inhibitor ramiprilat concentration-dependently increased the formation of cyclic GMP which was completely prevented by the stereospecific inhibitor of NO synthase, NG-nitro-L-arginine. Also the specific B2-kinin receptor antagonist icatibant (Hoe 140) abolished the increase in cyclic GMP as well as the ramiprilat-induced increase in PGI2 formation. The data demonstrate the existence of B2-kinin receptors and ACE activity in PBCEC. Moreover PBCEC are capable of producing and releasing kinins in amounts that lead via stimulation of B2-kinin receptors to an enhanced [Ca2+]i as well as NO and PGI2 synthesis and release, provided that degradation of kinins is prevented by inhibition of endothelial ACE activity.
authors.affiliation: Hoechst AG, SBU Cardiovascular Agents, Frankfurt/Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wiemer
authors.forename: R
authors.initials: R
authors.lastname: Popp
authors.forename: B A
authors.initials: BA
authors.lastname: Schölkens
authors.forename: H
authors.initials: H
authors.lastname: Gögelein
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002196:Capillaries; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D016257:Fura-2; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; C052549:ramiprilat; D001120:Arginine; D011464:Epoprostenol; D006152:Cyclic GMP; D017257:Ramipril; D001920:Bradykinin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D016257:Fura-2