Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs

Boaz Ovadia, Janine M. Bekker, Robert K. Fitzgerald, Alexander Kon, Stephan Thelitz, Michael J. Johengen, Karen Hendricks-Munoz, Rene Gerrets, Stephen M. Black, Jeffrey R. Fineman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial increase in pulmonary blood flow (PBF) that is followed by acute vasoconstriction. The objective of the present study was to determine the role of nitric oxide (NO)-endothelin-1 (ET-1) interactions in the acute changes in pulmonary vascular tone after in utero partial constriction of the DA. Twelve lategestation fetal lambs (132-140 days) were instrumented to measure vascular pressures and left PBF. After a 24-h recovery period, acute constriction of the DA was performed by partially inflating a vascular occluder, and the hemodynamic variables were observed for 4 h. In control lambs (n = 7), acute ductal constriction initially increased PBF by 627% (P < 0.05). However, this was followed by active vasoconstriction, such that PBF was restored to preconstriction values by 4 h. This was associated with a 43% decrease in total NO synthase (NOS) activity (P < 0.05) and a 106% increase in plasma ET-1 levels (P < 0.05). Western blot analysis demonstrated no changes in lung tissue endothelial NOS, preproET-1, endothelin-converting enzyme-1, or ET B receptor protein levels. The infusion of PD-156707 (an ET A receptor antagonist, n = 5) completely blocked the vasoconstriction and preserved NOS activity. These data suggest that the fetal pulmonary vasoconstriction after acute constriction of the DA is mediated by NO-ET-1 interactions. These include an increase in ET A receptor-mediated vasoconstriction and an ET A receptor-mediated decrease in NOS activity. The mechanisms of these NO-ET-1 interactions, and their role in mediating acute changes in PBF, warrant further studies.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number3 51-3
StatePublished - Jun 29 2002

Fingerprint

Endothelin-1
Constriction
Nitric Oxide
Ductus Arteriosus
Vasoconstriction
Lung
Nitric Oxide Synthase
Blood Vessels
Hemodynamics
Western Blotting
Pressure

Keywords

  • Ductus arteriosus
  • Pulmonary circulation

ASJC Scopus subject areas

  • Physiology

Cite this

Ovadia, B., Bekker, J. M., Fitzgerald, R. K., Kon, A., Thelitz, S., Johengen, M. J., ... Fineman, J. R. (2002). Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs. American Journal of Physiology - Heart and Circulatory Physiology, 282(3 51-3).

Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs. / Ovadia, Boaz; Bekker, Janine M.; Fitzgerald, Robert K.; Kon, Alexander; Thelitz, Stephan; Johengen, Michael J.; Hendricks-Munoz, Karen; Gerrets, Rene; Black, Stephen M.; Fineman, Jeffrey R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 282, No. 3 51-3, 29.06.2002.

Research output: Contribution to journalArticle

Ovadia, B, Bekker, JM, Fitzgerald, RK, Kon, A, Thelitz, S, Johengen, MJ, Hendricks-Munoz, K, Gerrets, R, Black, SM & Fineman, JR 2002, 'Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs', American Journal of Physiology - Heart and Circulatory Physiology, vol. 282, no. 3 51-3.
Ovadia B, Bekker JM, Fitzgerald RK, Kon A, Thelitz S, Johengen MJ et al. Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs. American Journal of Physiology - Heart and Circulatory Physiology. 2002 Jun 29;282(3 51-3).
Ovadia, Boaz ; Bekker, Janine M. ; Fitzgerald, Robert K. ; Kon, Alexander ; Thelitz, Stephan ; Johengen, Michael J. ; Hendricks-Munoz, Karen ; Gerrets, Rene ; Black, Stephen M. ; Fineman, Jeffrey R. / Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs. In: American Journal of Physiology - Heart and Circulatory Physiology. 2002 ; Vol. 282, No. 3 51-3.
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abstract = "Acute partial compression of the fetal ductus arteriosus (DA) results in an initial increase in pulmonary blood flow (PBF) that is followed by acute vasoconstriction. The objective of the present study was to determine the role of nitric oxide (NO)-endothelin-1 (ET-1) interactions in the acute changes in pulmonary vascular tone after in utero partial constriction of the DA. Twelve lategestation fetal lambs (132-140 days) were instrumented to measure vascular pressures and left PBF. After a 24-h recovery period, acute constriction of the DA was performed by partially inflating a vascular occluder, and the hemodynamic variables were observed for 4 h. In control lambs (n = 7), acute ductal constriction initially increased PBF by 627{\%} (P < 0.05). However, this was followed by active vasoconstriction, such that PBF was restored to preconstriction values by 4 h. This was associated with a 43{\%} decrease in total NO synthase (NOS) activity (P < 0.05) and a 106{\%} increase in plasma ET-1 levels (P < 0.05). Western blot analysis demonstrated no changes in lung tissue endothelial NOS, preproET-1, endothelin-converting enzyme-1, or ET B receptor protein levels. The infusion of PD-156707 (an ET A receptor antagonist, n = 5) completely blocked the vasoconstriction and preserved NOS activity. These data suggest that the fetal pulmonary vasoconstriction after acute constriction of the DA is mediated by NO-ET-1 interactions. These include an increase in ET A receptor-mediated vasoconstriction and an ET A receptor-mediated decrease in NOS activity. The mechanisms of these NO-ET-1 interactions, and their role in mediating acute changes in PBF, warrant further studies.",
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