title: Endothelial antioxidant actions of dihydropyridines and angiotensin converting enzyme inhibitors.
abstract: Dihydropyridines and angiotensin converting enzyme inhibitor effects on superoxide and nitric oxide (NO) were compared in high glucose (20 mM, 24 h)-treated human Ea.hy 926 endothelial cells. High glucose stimulated superoxide both extracellularly (lucigenin chemiluminescence, cytochrome c reduction) and intracellularly (dihydrorhodamine 123 fluorescence). The dihydropyridines amlodipine, nisoldipine, BayK 8644 or the angiotensin converting enzyme inhibitors captopril and enalaprilat attenuated extra- and intracellular superoxide formation; nifedipine blocked extracellular increases only, ramiprilat was without antioxidant effect. Dihydropyridines and captopril also prevented NADPH-driven superoxide release. Antioxidant actions were blunted by a bradykinin B(2) receptor antagonist or an inhibitor of p38 mitogen activated protein kinase (MAPK), and were accompanied by improved NO release (amperometric sensor). p38MAPK inhibition prevented the NO-sparing actions of dihydropyridines but not angiotensin converting enzyme inhibitors. Thus, dihydropyridines and angiotensin converting enzyme inhibitors limit high glucose-induced superoxide formation and improve NO bioavailability in human endothelial cells, in part via bradykinin and p38MAPK.
authors.affiliation: Department of Pharmacology, University Hospital Cologne, Germany. Anke.Rosenkranz@gmx.de
authors.forename: Anke C
authors.initials: AC
authors.lastname: Rosenkranz
authors.forename: Heinrich
authors.initials: H
authors.lastname: Lob
authors.forename: Thomas
authors.initials: T
authors.lastname: Breitenbach
authors.forename: Reinhard
authors.initials: R
authors.lastname: Berkels
authors.forename: Renate
authors.initials: R
authors.lastname: Roesen
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D004095:Dihydropyridines; D013481:Superoxides; D009569:Nitric Oxide; D045304:Cytochromes c; D005947:Glucose