Effect of ABT‐627 (A‐147627), a potent selective ETA receptor antagonist, on the cardiopulmonary profile of newborn lambs with surgically‐induced diaphragmatic hernia

Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right‐to‐left shunting. Endothelins (ETs) are potent vasoconstrictors and pro‐mitogenic peptides. Strong evidences support their participation in CDH and in th...

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Bibliographic Details
Published in:British journal of pharmacology 2001-12, Vol.134 (8), p.1679-1688
Main Authors: Kavanagh, Mélanie, Battistini, Bruno, Jean, Sonia, Crochetière, Josiane, Fournier, Louis, Wessale, Jerry, Opgenorth, Terry J, Cloutier, Raymond, Major, Diane
Format: Article
Language:English
Subjects:
ABT‐627
antagonist
Biological and medical sciences
Cardiovascular system
Congenital diaphragmatic hernia
endothelin receptors
endothelins
Medical sciences
Miscellaneous
Pharmacology. Drug treatments
pulmonary hypertension
right‐to‐left shunting
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Summary:Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right‐to‐left shunting. Endothelins (ETs) are potent vasoconstrictors and pro‐mitogenic peptides. Strong evidences support their participation in CDH and in the etiology of PH via the activation of ETA receptors (ETA‐Rs). Evaluation of the effect of ABT‐627, a selective non‐peptidic ETA‐R antagonist, given from −15 to 210 min post‐delivery (1 mg kg−1 bolus +0.01 mg kg−1 h−1 infusion, i.v.), was conducted in the lamb model of CDH. Severity of CDH was assessed in comparison to untreated controls (n=5). Untreated CDH lambs (n=7) had a higher mean pulmonary arterial pressure (MPAP; P
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704424