Increased concentrations of angiotensin-converting enzyme in the intimal hyperplasia of experimental vein grafts.
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).(ABSTRACT TRUNCATED AT 250 WORDS)
- [Show abstract] [Hide abstract]
ABSTRACT: Following vein grafting, responses in the arterial vein bypass grafts to angiotensin II, a known mitogen, increase. It is not known when these changes occur or whether these changes are due to alterations in endothelial cell function, excision/implantation of the vessel, or exposure to arterial hemodynamics. Two studies were designed to examine these questions. New Zealand White rabbits underwent excision of the external jugular vein, common carotid artery, an external jugular veno-venous bypass (VVG), or a common carotid veno-arterial bypass (VAG). Half the jugular veins and carotid arteries were mechanically denuded of their endothelium. All vein grafts were harvested at 28 days. A set of VAG was also harvested at 1, 3, 7, and 14 days. Isometric tension studies to angiotensin II (10(-10) to 10(-4) M) were performed on rings from each jugular vein, carotid artery, and vein graft. Jugular veins had a triphasic response to angiotensin II. Deendothelialized jugular veins had a triphasic response with an increased first phase and a much reduced second phase. Carotid arteries (6.87 +/- 0.18 and 6.15 +/- 0.18; with and without endothelium; means +/- SEM, -log10[EC50); p < .05), VVG (6.69 +/- 0.15), and VAG (7.42 +/- 0.29; p < .05 compared to VVG) showed a monophasic response to angiotensin II at 28 days. This monophasic response in VAG to angiotensin II was recordable at 7 days postoperatively and there was no further change in its sensitivity between 14 and 28 days. These results suggest that the induction of altered angiotensin II responses is dependent on exposure to the arterial circulation, that alterations in VAG responses occur within the first 7 days of vein grafting, and that VAG at 28 days become more sensitive to angiotensin II than the carotid vessels into which they are placed. These changes in smooth muscle cell sensitivity to a known smooth muscle cell mitogen (angiotensin II) may contribute to the development of intimal hyperplasia in the veno-arterial graft.Journal of Investigative Surgery 01/1996; 9(6):423-32. DOI:10.3109/08941939609025859 · 1.19 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The development of intimal hyperplasia in reversed vein grafts is associated with altered endothelial and vasomotor function. This study examines the effect of surgery on the morphology and vasomotor function of experimental arterial and venous vein bypass grafts. Twelve reversed vein grafts, 12 in situ vein grafts and 12 venovenous grafts were placed in 24 New Zealand White rabbits. All grafts remained patent and were harvested after 28 days. Isometric contraction to norepinephrine, histamine, bradykinin, serotonin and relaxation to acetylcholine and sodium nitroprusside following pre-contraction with prostaglandin F(2 alpha) were determined on the grafts and on contralateral jugular veins. Compared to the contralateral jugular veins, norepinephrine supersensitivity was induced in the reversed vein grafts, and venovenous vein grafts but not in the in situ vein grafts. Decrease in histamine sensitivity occurred in all grafted vessels. Bradykinin responses were significantly reduced in the in situ vein grafts and reversed vein grafts. Contractile responses to serotonin developed in the in situ vein grafts and reversed vein grafts only. Acetylcholine-induced endothelium-derived relaxing factor-mediated relaxation of the contralateral jugular veins was preserved in both venovenous grafts and in situ vein grafts but was lost in reversed vein grafts. All tissues relaxed to sodium nitroprusside in dose-dependent manner. The data suggest that norepinephrine supersensitivity in reversed vein grafts results from excision of the vessel. Attenuation of bradykinin responses and the enhanced contractile responses to serotonin appear predominantly to result from arterialization. Decreases in histamine sensitivity appear related both to excision and to arterialization. Neither the excision of the vein nor arterialization individually influences the alterations in endothelium-derived relaxing factor-mediated relaxation. However, a combination of excision and arterialization results in the altered endothelium-derived relaxing factor-mediated relaxation. This study suggests that the surgical preparation of the vein and the surgical procedure used have significantly different effects on endothelium-derived relaxing factor-mediated relaxation and smooth muscle contractility in vein grafts.Cardiovascular Surgery 05/1996; 4(2):150-60.
- [Show abstract] [Hide abstract]
ABSTRACT: The activity of the renin-angiotensin system may be important in determining the performance of coronary artery bypass grafts. We have examined the activity of tissue angiotensin-converting enzyme and the effects of angiotensin II in vessels used as bypass grafts. Organ bath studies were used to determine the vasoactive effect of angiotensin II. The activity of the angiotensin-converting enzyme was assessed by metabolism of a specific synthetic substrate. The saphenous vein produced greater maximum responses to angiotensin II than did the internal thoracic artery. This response was not modified by inhibition of nitric oxide synthase, cyclooxygenase, or by an endothelin receptor antagonist in either vessel. Losartan, an AT1 receptor antagonist, inhibited the vasoconstrictor response in both blood vessels. Homogenates of saphenous vein and internal thoracic artery displayed tissue angiotensin-converting enzyme activity, which was inhibited by captopril. Enzyme activity was threefold greater in the vein. Both the contractile response to angiotensin II and the enzyme activity were retained in venous grafts removed up to 20 years after coronary bypass surgery. These data demonstrate that marked differences exist in angiotensin-converting enzyme activity and AT1 receptor responses in the saphenous vein compared with the internal thoracic artery. These findings may have important implications for the performance of the vein when used as a coronary artery bypass graft and may have clinical implications for the use of angiotensin-converting inhibitors and AT1 receptor antagonists in the prevention and treatment of vein graft disease.Journal of Thoracic and Cardiovascular Surgery 09/1998; 116(2):206-12. DOI:10.1016/S0022-5223(98)70118-7 · 3.99 Impact Factor