Role of angiotensin-converting enzyme and neutral endopeptidase in flow-dependent remodeling

Vyacheslav A. Korshunov, Michael P. Massett, Robert M. Carey, Bradford C. Berk

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalJournal of Vascular Research
Volume41
Issue number2
DOIs
StatePublished - 2004

Keywords

  • Carotid artery
  • Fosinopril
  • Genetically hypertensive rats
  • Omapatrilat
  • Remodeling
  • cGMP

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