title: Endothelin-A receptor blockade and inhaled nitric oxide in a porcine model of meconium aspiration syndrome.
abstract: Acute neonatal pulmonary hypertension is associated with increased activation of the endogenous endothelin pathway. We investigated the role of selective endothelin-A receptor blockade using i.v. BQ-123 in a piglet model of meconium aspiration syndrome. Meconium aspiration was induced in 18 anesthetized piglets. Six controls received no further intervention. Six piglets received 1 mg/kg BQ-123 at 120 min, with the addition of 20 ppm inhaled nitric oxide at 240 min. Six commenced nitric oxide therapy at 120 min, and were given i.v. BQ-123 at 240 min. The total study duration was 360 min. Meconium aspiration resulted in acute pulmonary hypertension and elevated endothelin-1 levels in all animals. There were no changes in pulmonary hemodynamics or endothelin-1 levels beyond 120 min in controls. In the group receiving BQ-123 first, this agent alone reduced the pulmonary artery pressure and pulmonary vascular resistance, and the subsequent addition of inhaled nitric oxide further reduced pulmonary artery pressure. In the group first receiving nitric oxide alone, this reduced the pulmonary artery pressure, and the addition of BQ-123 resulted in a fall in pulmonary vascular resistance. Endothelin-1 levels increased with both agents. BQ-123 was found to be a highly effective pulmonary vasodilator and augmented the effects of nitric oxide in this model of acute pulmonary hypertension.
authors.affiliation: Paediatric Intensive Care Unit, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia. lara.shekerdemian@rch.org.au
authors.forename: Lara S
authors.initials: LS
authors.lastname: Shekerdemian
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Penny
authors.forename: Pia K
authors.initials: PK
authors.lastname: Ryhammer
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Reader
authors.forename: Hanne B
authors.initials: HB
authors.lastname: Ravn
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D065130:Endothelin A Receptor Antagonists; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D008471:Meconium Aspiration Syndrome; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism*; D013552:Swine; D013577:Syndrome
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D009569:Nitric Oxide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)