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

HERO ID

3078318

Reference Type

Journal Article

Subtype

Abstract

Year

2008

Language

English

HERO ID 3078318
Material Type Abstract
In Press No
Year 2008
Title Positive effects of PETN on endothelial function in hypertensive rats
Authors Oelze, M; Schuhmacher, S; Wenzel, P; Jansen, T; Stalleicken, D; Maethner, F; Kamuf, J; Sydow, L; Muenzel, T; Daiber, A
Journal Free Radical Biology and Medicine
Volume 45
Issue Suppl.
Page Numbers S148-S148
Abstract 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.
Wosid WOS:000260867900418
Url http://www.sciencedirect.com/science/article/pii/S0891584908006321
Is Certified Translation No
Dupe Override No
Conference Location Indianapolis, IN
Conference Name Society for Free Radical Biology and Medicine 15th Annual Meeting
Conference Date November 19-23, 2008
Is Public Yes
Language Text English
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