Development of the normal and hypertensive pulmonary vasculature

Normal adaptation to extra‐uterine life consists of an immediate increase in endothelial and smooth muscle cell (SMC) surface: volume ratio as the cells ‘spread’ in the vessel wall. Lumen diameter increases and resistance falls. Changes in SMC shape are associated with a transient depolymerization of contractile and cytoskeletal filaments. The four SMC phenotypes identified in the vessel wall rapidly show postnatal changes in the types of filament proteins and contractile‐associated proteins, indicating that the term ‘differentiation’ means little at this age. At birth, all SMCs have a predominantly synthetic phenotype. Endothelium‐dependent relaxation is relatively poor despite abundant nitric oxide synthase. SMCs are relatively insensitive to nitric oxide despite a high basal generation and a stimulated increase in cGMP generation. By contrast, the relaxation in response to ATP‐sensitive potassium (KATP) channel activation is present at birth, the response being similar to that seen in the adult. Neonatal pulmonary hypertension, due to either congenital heart disease or experimental chronic hypobaric hypoxia (51 kPa) is associated with abnormal structural remodelling. In experimental pulmonary hypertension, the normal maturation of endothelium‐dependent and ‐independent relaxation via soluble guanylate cyclase is delayed in newborns and the established responses are inhibited in older animals. The relaxant response to KATP channel activation is preserved. Thus, adaptation to extra‐uterine life consists of a rapid sequence of integrated morphological and functional changes, which is disturbed by the presence of pulmonary hypertension. The pattern of recovery from a pulmonary hypertensive insult is determined by the age at exposure and type and duration of the insult.