Original ArticleAngiotensin II Type 1 Receptor Blockade Does Not Enhance Apoptotic Cell Death During Ischemia and Reperfusion in Humans In VivoMeijer, Patrick MD*†; Wouters, Constantijn W MD*; Oyen, Wim J MD, PhD‡; Boerman, Otto C MD, PhD‡; Scheffer, Gert Jan MD, PhD†; Smits, Paul MD, PhD*§; Rongen, Gerard A MD, PhD*§Author Information From the Departments of *Pharmacology-Toxicology; †Anesthesiology; ‡Nuclear Medicine; and §Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Received for publication January 5, 2011; accepted March 5, 2011. Supported by an unrestricted research grant from Sanofi-Aventis. G.A. Rongen is a Clinical Established Investigator of the Netherlands Heart Foundation (2006 T035). C.W. Wouters is an MD medical research trainee funded by The Netherlands Organization for Health Research and Development (Project number: 920-03-353). The authors declare no conflicts of interest. Reprints: Gerard A. Rongen, MD, PhD, PO Box 9101, 6500 HB Nijmegen, The Netherlands (e-mail: G.Rongen@pharmtox.umcn.nl). Journal of Cardiovascular Pharmacology: June 2011 - Volume 57 - Issue 6 - p 702-706 doi: 10.1097/FJC.0b013e318218ef21 Buy Metrics Abstract Despite the theoretical benefits, angiotensin II type 1 receptor antagonists seem to enhance rather than reduce morbidity and mortality after myocardial infarction compared with angiotensin-converting enzyme inhibitors. This may result from unopposed angiotensin II type 2 receptor stimulation, which is associated with enhanced apoptotic cell death and increased infarct size. We studied whether the clinical effectiveness of irbesartan is hampered by enhanced apoptotic activity, detected by exposition of phosphatidylserines, during ischemia and reperfusion in humans in vivo. Twenty healthy male volunteers were randomized to a 1-week treatment with irbesartan (300 mg/d) or placebo in a double-blind fashion. After treatment, all participants underwent 10 minutes of ischemic exercise of the nondominant forearm. Upon reperfusion, Tc-99m-labeled Annexin A5 was administered, and 1 and 4 hours afterward, both hands were scanned using a gamma camera. Targeting of annexin A5, expressed as the percentage difference in radioactivity in the area of interest (thenar muscle) between experimental and control hand, did not differ between participants treated with irbesartan or placebo. Therefore, irbesartan does not enhance phosphatidylserine exposition in humans in vivo. The results of this study do not support enhanced apoptotic activity after treatment with irbesartan in a setting of ischemia and reperfusion. © 2011 Lippincott Williams & Wilkins, Inc.