Nitric Oxide and Pulmonary Hypertension

The pulmonary arterial vasculature, like the systemic arterial vasculature, is a dynamic system in which the resistance to blood flow is tightly regulated. Pathophysiologic states that perturb the normal control of pulmonary artery blood pressure result in significant clinical manifestations. The discovery of the central role of the nitric oxide (NO·) signal transduction system in the regulation of pulmonary arterial tone in health and disease has increased our understanding of the pathophysiology of pulmonary hypertension. In this chapter, we review (1) the causes, clinical manifestations, and epidemiology of pulmonary hypertension; (2) the biology of the NO·/cyclic guanosine monophosphate (cGMP) signal transduction system; (3) the production of NO· by NO synthase (NOS) isoforms in the lung and upper respiratory system and its regulation in fetal development; (4) the role of NO· in maintaining basal pulmonary vascular tone; (5) the role of NO· in modulating acute hypoxic pulmonary vasoconstriction; (6) the role of NO· in chronic pulmonary hypertension; (7) abnormalities of NO· production in human disease; and (8) the use of NO· and NO·-donor compounds for the diagnosis and treatment of pulmonary hypertension.