Loss of Tachyphylaxis and Increased Sensitivity to Angiotensin II in Experimental Vein Grants

Abstract

Intimal hyperplasia and atherosclerosis have been implicated in the pathophysiology of vein graft failure. Several recent studies have also reported alterations in the vasoreactivity of vein grafts. These alterations in vasoreactivity could contribute to vein graft spasm and lead to graft occlusion. This study examined the vasomotor responses of experimental vein grafts to angiotensin II, the most potent natural vasoconstrictor known. The right carotid artery was divided and bypassed in 12 rabbits with use of the right external jugular vein. The left external jugular vein was used as a control.

Eight vein grafts and jugular veins were harvested after fourteen days and 4 vein grafts after twenty-eight days. Segments of vein graft and control vein were mounted under isometric tension in an organ bath, and the dose response curves to angiotensin II obtained. On day 14, the response of the jugular veins was triphasic, while the respnse of the vein grafts was sigmoidal. The vein grafts were hypersensitive to angiotensin II. The ED₅₀ was reduced from 8.4 ± 2.5 x 10-6 M in the jugular veins to 1.62 ± 0.24 x 10^-8 M in the vein grafts (p < 0.005). The maximal response to angiotensin II was also increased from 342 ± 24 mg in the jugular veins to 558 ± 108 mg in the vein grafts on day 14 (p < 0.05). There was no significant difference in either the ED50 or the maximal response of the vein grafts on day 14 or 28. Tachyphylaxis (desensitization with repeated doses of agonist) was observed in the jugular veins but not in the vein grafts. The results show that experimental vein grafts are hypersensitive to angiotensin II, with either single or repeated exposure. This increased vasoreactivity to angiotensin II may have important clinical implications, particularly when vein grafts are used in patients with renovascular hypertension.