Regulation of vasodilator synthesis during lung development

The endothelium-derived vasodilator molecules prostaglandin I-2 (PGI(2)) an d nitric oxide (NO) are critically involved in the dramatic increase in pul monary blood flow that occurs during cardiopulmonary transition at birth. S tudies in animal and cell culture models have revealed that there is increa sed PGI(2) and NO production in the pulmonary circulation of the late fetus in direct response to increased oxygenation, and that this response is uni que to the pulmonary endothelium, Additional work; has demonstrated that th ere is normally marked upregulation in the expression of the key synthetic enzymes cyclooxygenase type I and endothelial NO synthase in the lung durin g late gestation, thereby maximizing the capacity for vasodilator productio n at the time of birth. Furthermore, studies in animal models of neonatal p ulmonary hypertension indicate that attenuated expression of these genes ma y frequently contribute to the pathogenesis of the disorder. A greater unde rstanding of the mechanisms regulating PGI(2) and NO synthesis in the devel oping lung will potentially lead to novel therapies for neonatal pulmonary hypertension aimed at optimizing endogenous vasodilator production. (C) 199 9 Elsevier Science ireland Ltd. All rights reserved.