Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Research Paper J Vasc Res 2010;47:336–345 DOI: 10.1159/000265567 Autonomous Effects of Shear Stress and Cyclic Circumferential Stretch regarding Endothelial Dysfunction and Oxidative Stress: An ex vivo Arterial Model Tyler N. Thacher a Paolo Silacci d Nikos Stergiopulos a Rafaela F. da Silva a–c a Laboratory of Hemodynamics and Cardiovascular Technology, Swiss Federal Institute of Technology, Lausanne, b Department of Neurosurgery, Geneva University Hospital, and c Department of Neurosciences, University Medical Center, University of Geneva Medical School, Geneva, and d Station de recherche Agroscope Liebefeld, Posieux, Switzerland modulated more significantly by reduced cyclic stretch than by oscillatory shear, emphasizing an important distinction between shear- and stretch-mediated effects to the vascular wall. Western blotting analysis of eNOS and nitrotyrosine proved that they too are more significantly negatively mod- ulated by oscillatory flow than by reduced stretch. These findings point out how shear and stretch stimulate regions of the vascular wall differently, affecting NO bioavailability and contributing to vascular disease. Copyright © 2009 S. Karger AG, Basel Introduction Within the vasculature, endothelial cells are constant- ly exposed to dynamic mechanical forces generated by pulsatile blood flow. Two such stimuli known to modu- late endothelial function are shear stress and cyclic cir- cumferential strain. It has been documented that areas of the vasculature exposed to low mean shear stress and cy- clic reversal of flow direction (also called oscillatory flow, Key Words Endothelial dysfunction  Nitrotyrosine  Oxidative stress  Cyclic stretch and shear stress Abstract Cyclic circumferential stretch and shear stress caused by pul- satile blood flow work in concert, yet are very different stim- uli capable of independently mediating endothelial func- tion by modulating eNOS expression, oxidative stress (via production of superoxide anion) and NO bioavailability. Por- cine carotid arteries were perfused using an ex vivo arterial support system for 72 h. Groups we created by combining normal (5%) and reduced (1%) stretch with high shear (6 8 3 dynes/cm 2 ) and oscillatory shear (0.3 8 3 dynes/cm 2 ) stress while maintaining a pulse pressure of 80 8 10 mm Hg. Oscil- latory flow and reduced stretch both proved detrimental to endothelial function, whereas oscillatory flow alone domi- nated total endogenous vascular wall superoxide anion pro- duction. Yet, when superoxide anion production was ana- lyzed in just the endothelial region, we observed that it was Received: January 19, 2009 Accepted after revision: June 24, 2009 Published online: December 16, 2009 Dr. Tyler Thacher Laboratoire d’Hémodynamique et de Technologie Cardiovasculaire École Polytechnique Fédéral de Lausanne Bâtiment AI 1241, Station 15, CH–1015 Lausanne (Switzerland) Tel. +41 21 693 9654, Fax +41 21 693 9635, E-Mail tyler.thacher @ epfl.ch © 2009 S. Karger AG, Basel 1018–1172/10/0474–0336$26.00/0 Accessible online at: www.karger.com/jvr