Chronic rejection of rat aortic allografts: effect of inhibition of the thromboxane cascade

Non-immunosuppressed rat aortic allografts from DA (RT1^av1) to WF (RT1^u) strain develop, after a short reversible acute rejection episode, chronic arteriosclerotic changes in the vascular wall, which are indistinguishable from those seen in human allografts during chronic rejection [1]. Incubation of the aortic wall segments in vitro and immunochemical assays demonstrated that the allografts synthesized increased amounts of TxB2, but not 6-keto-PGF_1α or LTB4, compared to syngenic or normal aortas. The two major cellular components of the vascular wall, intima and adventitia, were incubated separately after microdissection. TxB2 was produced in the adventitia, whereas most of the 6-keto-PGF₁α was synthesized in the intima. Administration of a specific TxA2 receptor inhibitor to the recipient rat reduced significantly the proliferation of adventitial inflammatory cells and the intimal smooth muscle cells. Nevertheless, it only delayed but did not inhibit the overall sclerosis of the intima.