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Vol. 41, No. 2, 2004
Issue release date: March–April 2004
Section title: Research Paper
J Vasc Res 2004;41:148–156
(DOI:10.1159/000077144)

Role of Angiotensin-Converting Enzyme and Neutral Endopeptidase in Flow-Dependent Remodeling

Korshunov V.A. · Massett M.P. · Carey R.M. · Berk B.C.
aCenter for Cardiovascular Research and Department of Medicine, University of Rochester, Rochester, N.Y., and bDepartment of Internal Medicine, University of Virginia Health System, Charlottesville, Va., USA

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: 7/16/2003
Accepted: 9/30/2003
Published online: 4/21/2004

Number of Print Pages: 9
Number of Figures: 9
Number of Tables: 3

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR

Abstract

Omapatrilat inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). We compared the effects of omapatrilat (40 mg/kg/day, p.o.) to fosinopril (40 mg/kg/day, p.o.) on flow-induced vascular remodeling in New Zealand genetically hypertensive (GH) rats. Both drugs equally reduced blood pressure (BP) initially, but systolic BP and pulse pressure were reduced more by omapatrilat after 1 week. Carotid remodeling was induced by partial ligation of the left common carotid artery (LCA). There was little remodeling in untreated GH rats – measured as outer diameter to body weight (OD/BW vs. before ligation): 97 ± 1% of initial LCA (low flow) and 107 ± 3% of initial right common carotid artery (RCA, high flow). In contrast, OD/BW increased to 118 ± 5% (p < 0.05) of initial RCA after omapatrilat versus 108 ± 2% (p = 0.96) after fosinopril. The major change was increased RCA lumen area which was significantly larger in omapatrilat-treated animals (127% vs. control) than fosinopril-treated animals (103% vs. control). The increase in outward remodeling after omapatrilat treatment correlated weakly with vascular cGMP levels and decreased systolic BP. The results suggest that dual inhibition of NEP/ACE may have greater effects than ACE inhibition alone on vessel remodeling in hypertension.


  

Author Contacts

Dr. Bradford C. Berk
University of Rochester, Center for Cardiovascular Research
601 Elmwood Avenue
Rochester, NY 14642 (USA)
Tel. +1 585 273 1946, Fax +1 585 273 1497, E-Mail Bradford_Berk@URMC.rochester.edu

  

Article Information

Received: July 16, 2003
Accepted after revision: September 30, 2003
Published online: March 3, 2004
Number of Print Pages : 9
Number of Figures : 9, Number of Tables : 3, Number of References : 28

  

Publication Details

Journal of Vascular Research (Incorporating International Journal of Microcirculation)
Founded 1964 as Angiologica by M. Comèl and L. Laszt (1964–1973) continued as Blood Vessels by J.A. Bevan (1974–1991)
Official Journal of the European Society for Microcirculation

Vol. 41, No. 2, Year 2004 (Cover Date: March-April 2004)

Journal Editor: U. Pohl, Munich
ISSN: 1018–1172 (print), 1423–0135 (Online)

For additional information: http://www.karger.com/jvr


Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: 7/16/2003
Accepted: 9/30/2003
Published online: 4/21/2004

Number of Print Pages: 9
Number of Figures: 9
Number of Tables: 3

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR


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