Pharmacological and biochemical studies on the contribution of NADPH oxidase to oxidative stress in the aorta of spontaneously hypertensive rats [Elektronische Ressource] / vorgelegt von Sven Wind

PHARMACOLOGICAL AND BIOCHEMICAL STUDIES ON THE CONTRIBUTION OF NADPH OXIDASE TO OXIDATIVE STRESS IN THE AORTA OF SPONTANEOUSLY HYPERTENSIVE RATS Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften (Dr. rer. nat.) dem Fachbereich Pharmazie der Philipps-Universität Marburg vorgelegt von Sven Wind aus Dillenburg Marburg/Lahn 2006 I Vom Fachbereich Pharmazie der Philipps-Universität Marburg als Dissertation am _____________________________angenommen. Erstgutachter: Prof. Dr. Harald H. H. W. Schmidt Zweitgutachter: Prof. Dr. Dr. Josef Krieglstein Tag der mündlichen Prüfung: ____________________________________II für Alexandra III CONTENT 1 INTRODUCTION 1 2 SCIENTIFIC BACKGROUND 2 2.1 Oxidative stress and the biology of reactive oxygen species 2 2.2 Effects of ROS in the vasculature 4 2.3 Sources of ROS in the vasculature 5 2.3.1 Xanthine oxidase 5 2.3.2 Endothelial NO synthase 6 2.3.3 NADPH oxidases 7 2.3.4 The “kindling bonfire” hypothesis 7 2.4 NADPH oxidases 9 2.4.1 Structure 9 2.4.2 Expression of subunits in the vasculature 12 2.4.3 Activation of the phagocytic NADPH oxidase 13 2.4.4 Activation of vascular NADPH oxidases 14 2.4.5 Pharmacology of NADPH oxidases 15 2.5 ROS and vascular diseases 19 3 AIMS OF THE STUDY 22 4 MATERIALS AND METHODS 23 4.1 Chemicals 23 4.2 Devices and software 25 4.2.1 Devices 25 4.2.