Developmental effects of endothelin-1 on the pulmonary circulation in sheep

Jackson Wong, Paula Vanderford, Jeffrey R. Fineman, Scott J. Soifer

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) is a polypeptide that has potent hemodynamic effects on the pulmonary circulation. To determine whether there are changes in these effects with increasing postnatal age, we investigated the effects of ET-1 (250 ng/kg) at rest and during pulmonary hypertension in eight lambs (<1 wk old) and 11 juvenile sheep (6-12 mo old). At rest, ET-1 did not change pulmonary arterial pressure in lambs, but increased pulmonary arterial pressure by 64.0 ± 37.5% (p <0.05) in sheep. During pulmonary hypertension, ET-1 produced greater decreases in pulmonary arterial pressure in lambs than in sheep (26.6 ± 3.4% versus 18.7 ± 8.3%, p <0.05). In juvenile sheep, the increase in resting pulmonary arterial pressure produced by ET-1 was inhibited by meclofenamic acid, an inhibitor of prostaglandin synthesis (40.3 ± 9.9% versus 2.3 ± 4.7%, p <0.05); during pulmonary hypertension, the decrease in pulmonary arterial pressure produced by ET-1 was inhibited by Nω-nitro-L-arginine, an inhibitor of endothelium-derived nitric oxide synthesis (21.4 ± 10.7% versus 8.0 ± 3.6%, p <0.05) and by glybenclamide, an ATP-dependent potassium-channel blocker (18.8 ± 8.4% versus 4.0 ± 4.4%, p <0.05). The hemodynamic effects of ET-1 on the pulmonary circulation are dependent on postnatal age. Pulmonary vasoconstriction is mediated by prostaglandin production, and pulmonary vasodilation is mediated, in part, by release of endothelium-derived nitric oxide and activation of ATP-dependent potassium channels.

Original languageEnglish (US)
Pages (from-to)394-401
Number of pages8
JournalPediatric Research
Volume36
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

Pulmonary Circulation
Endothelin-1
Sheep
Lung
Arterial Pressure
Pulmonary Hypertension
Nitric Oxide
Adenosine Triphosphate
Hemodynamics
Potassium Channel Blockers
Meclofenamic Acid
Prostaglandin Antagonists
Glyburide
Potassium Channels
Vasoconstriction
Vasodilation
Prostaglandins
Arginine
Peptides

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Developmental effects of endothelin-1 on the pulmonary circulation in sheep. / Wong, Jackson; Vanderford, Paula; Fineman, Jeffrey R.; Soifer, Scott J.

In: Pediatric Research, Vol. 36, No. 3, 1994, p. 394-401.

Research output: Contribution to journalArticle

Wong, J, Vanderford, P, Fineman, JR & Soifer, SJ 1994, 'Developmental effects of endothelin-1 on the pulmonary circulation in sheep', Pediatric Research, vol. 36, no. 3, pp. 394-401.
Wong, Jackson ; Vanderford, Paula ; Fineman, Jeffrey R. ; Soifer, Scott J. / Developmental effects of endothelin-1 on the pulmonary circulation in sheep. In: Pediatric Research. 1994 ; Vol. 36, No. 3. pp. 394-401.
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