Modulation of Nitric Oxide Release in Perinatal Lung

Abstract

After completing this article, readers should be able to: 1. Describe transitional changes in fetal pulmonary circulation at birth. 2. Delineate the role of nitric oxide in pulmonary vasodilation at birth. 3. List the factors that stimulate nitric oxide release at birth. 4. Describe the role of oxidative phosphorylation and adenosine triphosphate in the stimulation of nitric oxide release at birth. 5. Classify purine receptors and their functions in the fetal cardiovascular system. The lung in the fetus is a liquid-filled organ that has high resistance to pulmonary blood flow. Rapid adaptation of the fetal lung to the extrauterine environment is essential to ensure survival of the newborn. Gas exchange is established at birth when air enters the alveolar space and pulmonary blood flow increases nearly tenfold to provide the optimum ventilation/perfusion match. A rapid and sustained decrease in pulmonary vascular resistance (PVR) facilitates this postnatal adaptation. The pulmonary vasodilation is initiated by a number of birth-related stimuli, such as distension of the lung,1 increase in oxygen tension,2 establishment of air-liquid interface, and hemodynamic shear stress. Oxygen appears to be the most important of these birth-related stimuli in causing pulmonary vasodilation as the fetus makes the transition from a low to a high o2 environment (Fig. 1⇓ ).2 Preparation of the pulmonary vascular bed for this event begins before birth, with a gradual increase in pulmonary blood flow and reactivity of pulmonary vessels to oxygen being demonstrated in late gestation.3 Figure 1. Changes in alveolar and arterial Po2 (torr). Although the precise mechanisms that regulate pulmonary vasodilation are not known, studies in fetal lambs have demonstrated that vascular endothelium plays a major role by releasing nitric oxide (NO)4,5 and vasodilator prostaglandins6 at birth. The expression of endothelial nitric oxide synthase (eNOS) enzyme undergoes a developmental …