INCREASED CONCENTRATIONS OF ANGIOTENSIN-CONVERTING ENZYME IN THE INTIMAL HYPERPLASIA OF EXPERIMENTAL VEIN GRAFTS

Local renin and angiotensin-converting enzyme (ACE) activity were rece ntly implicated in development of intimal hyperplasia after vascular i njury, but little is known about the local responses of angiotensin I/ II (AI/AII) and local ACE activity in vein graft physiology. The activ ity of the local ACE system of experimental vein grafts was examined i n 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 graft s were harvested after 14 days. Rings from both vessels were studied i n vitro under isometric tension, and dose-response curves to AI and AI I were obtained. AI responses were also measured in the presence of ca ptopril. The tissue concentrations of ACE in both vessels were estimat ed by spectrophotometry and were localized by immunohistochemistry. Th e responses of the veins to AI and AII were multiphasic, whereas the r esponses of vein grafts were sigmoid-shaped. Incubation of vein grafts with captopril significantly decreased the sensitivity to AI (p < 0.0 001). Immunohistochemical localization identified ACE in the endotheli al layer of the veins and vein grafts, but also at a greater density i n 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). T hese results indicate that increased levels of ACE in experimental vei n 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 angi otensin systems may modulate the proliferative response that follows g rafting and may explain the efficacy of ACE inhibition in controlling intimal hyperplasia.