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DOI: 10.1055/s-2005-923325
© Georg Thieme Verlag Stuttgart · New York
Oxidativer Stress und kardiovaskuläre Erkrankungen
Oxidative stress and cardiovascular diseasesPublikationsverlauf
eingereicht: 28.6.2005
akzeptiert: 20.10.2005
Publikationsdatum:
12. Dezember 2005 (online)
Zusammenfassung
Für eine Vielzahl von kadiovaskulären Erkrankungen konnte nachgewiesen werden, dass die Bildung von Radikalen (oxidativer Stress) zur Pathogense bzw. Progression dieser Prozesse beiträgt. Beispiele hierfür sind Hypercholesterolämie und Atherosklerose sowie Hypertonie, Diabetes und verschiedene durch Ischämie-Reperfusionsschäden bedingte Herzerkrankungen. Im Besonderen wird auf Superoxid eingegangen, da ihm eine zentrale Rolle bei der Modulation des peripheren Gefäßwiderstandes zukommt, indem es den stets wirksamen endogengebildeten Vasodilatator Stickstoffmonoxid (NO) abfängt, zum stark oxidativen Peroxynitrit umwandelt und damit eine endotheliale Dysfunktion auslösen kann. Hier soll eine Übersicht über die zugrunde liegenden Mechanismen des erhöhten oxidativen Stresses gegeben sowie aufgezeigt werden, über welche antioxidativen Komponenten die verschiedenen Pharmaka in das Redoxgleichgewicht eingreifen und so als zusätzlichen protektiven Effekt den oxidativen Stress absenken können. Im Besonderen wird auf unterschiedlich wirksame organische Nitrate eingegangen und diskutiert, wie diese einerseits oxidativen Stress und dadurch eine Nitrattoleranz induzieren und andererseits diesen Prozessen sogar entgegenwirken.
Summary
A number of diseases like hypercholesterolemia and atherosclerosis, hypertension, congestive heart failure, diabetes, ischemia-reperfusion, neurodegenerative diseases as well as acute and chronic inflammatory diseases are characterized by an increased steady-state concentration of reactive oxygen species (ROS). On a biomolecular level an enhanced oxidative stress causes damage of proteins, lipids and nucleic acids. Both the experimental and therapeutic efficiency of different antioxidative compounds (like various antioxidative enzymes) , drugs, metabolites and vitamins for the maintenance of an appropriate intracellular redox potential underline the importance of an excessive ROS-formation for these diseases. Control of excessive ROS-formation can be obtained by angiotensin converting enzyme (ACE-) inhibitors, by AT1-receptor blockers, by statins and other lipid lowering compounds, by improved expression of antioxidative enzymes (superoxide dismutase, catalase etc.), by compounds such as probucol, certain vitamins, pyruvate, by lipid apheresis and by physical exercise training, which displays surprising efficacy.
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Prof. Dr. E. Bassenge
Albert-Ludwigs Universität, Institut für Angewandte Physiologie
Hermann-Herder-Straße 9
79104 Freiburg
Telefon: 07633 6590
Fax: 07633 6590
eMail: angphys@ruf.uni-freiburg.de