Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1

Cheryl C. Docherty, Judit Kalmar-Nagy, Marc Engelen, Steven V. Koenen, Mark Nijland, Rhoda E. Kuc, Anthony P. Davenport, Peter W. Nathanielsz

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

At 110-111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 μg·kg-1·h-1 iv) for 48 h. Measurement of fetal blood pressure showed a greater increase in dexamethasone-treated (n = 6) compared with control (n = 5) fetuses (7.3 ± 2.3 vs. 0.6 ± 2.3 mmHg, P < 0.05). Fetuses were delivered by cesarean section, and the femoral muscle and brain were obtained under halothane anesthesia. Femoral and middle cerebral arteries (∼320-μm internal diameter) were evaluated using wire myography. Sensitivity to KCl (2.5-125 mM) and the magnitude of the maximal vasoconstriction to 125 mM K+ were similar in femoral and middle cerebral arteries from dexamethasone-treated vs. control fetuses. Acetylcholine-induced vasorelaxation was similar in femoral arteries from control and dexamethasone-treated fetuses. Middle cerebral arteries did not relax to acetylcholine. Sensitivity to endothelin-1 (ET-1; 0.1 pM-0.1 μM) and magnitude of the ET-1-induced vasoconstriction were greater in femoral arteries from dexamethasone-treated vs. control fetuses (P < 0.05). Autoradiographical studies with receptor-specific ligands demonstrated increased ETA-receptor binding, the principal receptor subtype, in femoral muscle vessels (P < 0.001) but decreased ETA-receptor binding in middle cerebral arteries (P < 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ETB-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ETA-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.

Original languageEnglish (US)
Pages (from-to)R261-R268
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number1 50-1
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Blood pressure
  • Fetal sheep
  • Glucocorticoids

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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