Transplant arteriopathy: Role of nitric oxide synthase

Endothelial vasodilator dysfunction is a major manifestation of transplant arteriopathy. This impairment reflects abnormalities in the production or activity of several endothelial vasoactive substances. Most notably, there is a significant deficit in the nitric oxide synthase (NOS) pathway. The impairment of the NOS pathway contributes to alterations in vascular reactivity, structure, and interaction with circulating factors. Since endothelium-derived NO suppresses vascular cell proliferation and vascular inflammation, a deficit in vascular NO facilitates the initiation and progression of transplant arteriopathy. The allograft endothelium is made dysfunctional by a number of factors including ischemia-reperfusion during transplantation; metabolic abnormalities posttransplantation including dyslipidemia, insulin resistance, and hypertension due to the use of immunosuppressive agents; the direct effects of some immunosuppressive agents on endothelial function; and infectious agents, most notably cytomegalovirus (CMV). This chapter focuses on factors adversely influencing endothelial dysfunction in transplant arteriopathy. The further delineation of the mechanisms by which the NOS pathway becomes dysregulated in transplant arteriopathy will be useful in the pursuit of new diagnostic and therapeutic modalities.