ETA-receptor blockade and ETB-receptor stimulation in experimental congenital diaphragmatic hernia

The aim of this study was to assess the role of nitric oxide (NO) and endot helin (ET)-1 in the pathophysiology of persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created congenital diaphragma tic hernia (CDH). The pulmonary vascular response to various agonists and a ntagonists was assessed in vivo between 128 and 132 days gestation. Age-mat ched fetal lambs served as control animals. Control and CDH lambs had simil ar pulmonary vasodilator responses to acetylcholine, sodium nitroprusside, zaprinast, and dipyridamole. The ETA-receptor antagonist BQ-123 caused a si gnificantly greater pulmonary vasodilatation in CDH than in control animals . The ETB-receptor agonist sarafotoxin 6c induced a biphasic response, with a sustained pulmonary vasoconstriction after a transient pulmonary vasodil atation that was not seen in CDH animals. We conclude that the NO signaling pathway in vivo is intact in experimental CDH. In contrast, ETA-receptor b lockade and ETB-receptor stimulation significantly differed in CDH animals compared with control animals. Imbalance of ET-l-receptor activation favori ng pulmonary vasoconstriction rather than altered NO-mediated pulmonary vas odilatation is likely to account for persistent pulmonary hypertension of t he newborn in fetal lambs with a surgically created CDH.