Endothelial antioxidant actions of dihydropyridines and angiotensin converting enzyme inhibitors.
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.
Rosenkranz
Anke C
AC
Department of Pharmacology, University Hospital Cologne, Germany. Anke.Rosenkranz@gmx.de
Lob
Heinrich
H
Breitenbach
Thomas
T
Berkels
Reinhard
R
Roesen
Renate
R
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*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D004095:Dihydropyridines; D013481:Superoxides; D009569:Nitric Oxide; D045304:Cytochromes c; D005947:Glucose