PULMONARY VASCULAR BALANCE IN CONGENITAL DIAPHRAGMATIC-HERNIA - ENHANCED ENDOTHELIN-1 GENE-EXPRESSION AS A POSSIBLE CAUSE OF PULMONARY VASOCONSTRICTION

Background: Pulmonary hypoplasia and persistent pulmonary hypertension (PPH) are the principal causes of the ongoing mortality in congenital diaphragmatic hernia (CDH) presenting with respiraton/insufficiency w ithin 6 hours after birth. Endothelin-l (ET-1) is an endothelial-deriv ed vasoconstrictor, which could play an important role in modulating p ulmonary vascular tone in PPH. ET-1 exerts its role in controling vasc ular tone through two different subtype receptors, endothelin-A recept or (ETA) which is responsible for vasoconstriction and endothelin-B re ceptor (ETB) which is responsible for vasodilatation by induction of n itric oxide synthase. Methods: We examined the pulmonary expression of ET-1, ETA and ETB mRNAs in a rat model of CDH. CDH was induced in rat s by administration of 100 mg of nitrofen dissolved in olive oil on da y 10 of gestation. Fetal lungs were collected after cesarean section o n gestational day 22 (term) and processed for Northern blot analysis a nd quantitative polymerase chain reaction (PCR). Results: Significantl y (P < .05) enhanced levels of ET-1 mRNA were observed in CDH rats com pared with control rats. In contrast to equal levels of ETB mRNA, a tw o-to fourfold increase in ETA mRNA levels were observed in CDH as comp ared with control rats. Conclusions: The upregulated expression of ET- 1 and ETA receptor mRNA before birth strongly support the reason for p ulmonary vasoconstriction and altered pulmonary vascular muscularizati on in CDH. Consequently in the clinical setting, the use of endothelin receptor blockade for the treatment of PPH may be considered against the background of the unpredictable and variable response to inhaled n itric oxide in newborns with CDH. Copyright (C) 1998 by W.B. Saunders Company.