Kinetics of Altered Angiotensin II Responses in Experimental Vein Grafts

Abstract

Following vein grafting. responses in the arterial vein bypass grafis 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/imphtation 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 endotheliwn. 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

Key Words:

• angiotensin II
• endothelium
• smooth muscle cells
• vein grafts