Nitric oxide signaling in vascular biology.

Nitric oxide (NO) research has expanded rapidly in the past 20 years, and the role of NO in physiology and pathology has been extensively studied. This review focuses on the pathways of NO synthesis and metabolism in vascular biological systems. Healthy vascular homeostasis is dependent on the integrity of the endothelium, which is a very large dynamic autocrine and paracrine organ with vasodilator, anti-inflammatory, and antithrombotic properties. The importance and relevance of NO signaling is stressed in this review. The potential role of nitrotyrosine formation with vascular pathological conditions is discussed. The use of pharmacologic, biochemical, and molecular biological approaches to characterize, purify, and reconstitute these regulatory pathways should lead to the development of new therapies for various pathological conditions that are characterized by an insufficient production of NO. With more than 77,000 publications in the field of NO signaling, this brief review can only focus on some aspects of the field as it applies to vascular biology. Many molecular targets have been identified for drug development dealing with NO and cyclic guanosine monophosphate formation, metabolism, and function. Many agents have been identified that are in pre-clinical evaluation or in clinical trials. Certainly, many should prove to be important therapeutic additions during the next decade.