Mechanisms of dysfunction of the nitric oxide pathway in vascular diseases

Vascular nitric oxide (NO) is involved in many physiologic and pathophysiologic processes throughout the body. Many vascular diseases have a reduction in the activity of endothelium-derived NO as an important component involved in the initiation and/or progression of the disease. It is now known that there are multiple mechanisms for this reduction in NO activity with one or more mechanisms operating depending on the specific condition or stage of a disease. In other instances, the therapy for certain diseases is responsible for the reduction in NO activity and contributes to the acceleration of vascular disease. This review details the known mechanisms of dysfunction of the NO pathway leading to vascular diseases, which provides the rationale for why certain therapies can improve while other therapies adversely affect vascular health.