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

Abstract

At 110-111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 microgram. 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 (approximately 320-micrometer 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 microM) 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 ET(A)-receptor binding, the principal receptor subtype, in femoral muscle vessels (P < 0.001) but decreased ET(A)-receptor binding in middle cerebral arteries (P < 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ET(B)-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ET(A)-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.

Endothelin‐induced constriction of the ductus venosus in fetal sheep: developmental aspects and possible interaction with vasodilatory prostaglandin

“…TXA 2 , on the other hand, is as potent as ET-1 in contracting the ductus (Adeagbo et al, 1985;see Results), but in exerting any effect it may only originate from extramural sources (Adeagbo et al, 1982;1985). Significant in the present context is also the observation that corticosteroids, while enhancing the susceptibility of fetal blood vessels to ET-1 (Docherty et al, 2001), are also capable of promoting the closure of the ductus in the prematurely born infant (Kondo et al, 2001). In addition, tests with big ET-1, specifically the demonstration of the susceptibility of the agent to the interfering action of phosphoramidon, point to the occurrence of a functional converting enzyme in the tissue.…”

Antenatal Corticosteroids Increase Fetal, But Not Postnatal, Pulmonary Blood Flow in Sheep

“…resistance (22,23) and decrease cerebral blood flow by increasing cerebral vascular resistance (15). Corticosteroids have also been shown to influence the fetal pulmonary circulation by enhancing its adaptation at birth.…”

Early gestation dexamethasone programs enhanced postnatal ovine coronary artery vascular reactivity

“…Late prenatal glucocorticoid exposure also results in fetal hypertension and enhances the contractile response of femoral arteries to endothelin and depolarizing potassium solutions, while attenuating the vasodilator effects of forskolin and bradykinin (1,6). However, late-gestation corticosteroid exposure fails to program the development of hypertension during postnatal life (17).…”