Increased concentrations of angiotensin-converting enzyme in the intimal hyperplasia of experimental vein grafts

M. K. O'Donohoe, M. G. Davies, Z. S. Radic, E. M. Mikat, P. O. Hagen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Local renin and angiotensin-converting enzyme (ACE) activity were recently implicated in development of intimal hyperplasia after vascular injury, but little is known about the local responses of angiotensin I/II (AI/AII) and local ACE activity in vein graft physiology. The activity of the local ACE system of experimental vein grafts was examined in this study. The right carotid artery was divided and bypassed in 21 New Zealand White rabbits, using the right external jugular vein. The left external jugular vein was used as a control. Veins and vein grafts were harvested after 14 days. Rings from both vessels were studied in vitro under isometric tension, and dose- response curves to AI and AII were obtained. AI responses were also measured in the presence of captopril. The tissue concentrations of ACE in both vessels were estimated by spectrophotometry and were localized by immunohistochemistry. The responses of the veins to AI and AII were multiphasic, whereas the responses of vein grafts were sigmoid-shaped. Incubation of vein grafts with captopril significantly decreased the sensitivity to AI (p < 0.0001). Immunohistochemical localization identified ACE in the endothelial layer of the veins and vein grafts, but also at a greater density in the intimal hyperplasia of the vein graft. The concentration of ACE was 1.92 ± 0.16 U/g (wet weight; mean ± SEM, n = 9) in vein grafts and 1.39 ± 0.05 U/g in the veins (38% increase, p < 0.05, n = 9). These results indicate that increased levels of ACE in experimental vein grafts are associated with altered responses to AI and AII and that ACE is predominantly localized to the intimal hyperplastic layer. The increased concentration of ACE in vein grafts suggests that local angiotensin systems may modulate the proliferative response that follows grafting and may explain the efficacy of ACE inhibition in controlling intimal hyperplasia.

Original languageEnglish (US)
Pages (from-to)594-601
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume23
Issue number4
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • Angiotensin
  • Angiotensin-converting enzyme
  • Function
  • Histology
  • Smooth muscle cells
  • Vein grafts

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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