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3078318 
Journal Article 
Abstract 
Positive effects of PETN on endothelial function in hypertensive rats 
Oelze, M; Schuhmacher, S; Wenzel, P; Jansen, T; Stalleicken, D; Maethner, F; Kamuf, J; Sydow, L; Muenzel, T; Daiber, A 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S148-S148 
English 
WOS:000260867900418 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
In contrast to other organic nitrates pentaerithrityl tetranitrate (PETN)-treatment in Wistar rats induces neither nitrate tolerance nor cross-tolerance, which can be explained by induction of antioxidant mechanisms like heme oxygenase-1 (HO-1) and Ferritin. With the present studies we tested in an animal model of angiotensin-II (AT-II) induced hypertension, whether chronic treatment with PETN will preserve its beneficial effects compared to the effects of chronic treatment with Isosorbitmononitrate (ISMN). Therefore male wistar rats (230-250 g) were treated with AT-II (1 mg/kg/d) alone or together with PETN (15 mg/kg/d) or ISMN (75 mg/kg/d) via subcutaneous osmotic minipumps for 7 days. Control pumps were applied with the solving reagent, respectively. Ang-II infusion caused endothelial dysfunction and reduced endothelial independent relaxation, indicated by a decreased vasodilator potency of acetylcholine and nitroglycerin in isolated aortic rings, an increase of reactive superoxide species (ROS) in aortic vessels and in NADPH oxidase activity in heart membrane fractions, as detected by lucigenin- (5µM) derived chemiluminescence (LDCL). Staining of aortic sections and HPLC-derived measurements with the fluorescent dye dihydroethidine showed O2− formation throughout the vessel wall. In addition, expression of HO-1 was increased in aorta. in contrast to ISMN, co-treatment with PETN normalized in part vascular function and ROS-formation. Furthermore, HO-1 expression was further enhanced by PETN, not by ISMN. Thus, the beneficial effects of PETN on AT-II induced hypertension may be also explained by induction of antioxidant mechanisms and thereby its preserved nitrovasodilatory action. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008