Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1.
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.
Docherty
C C
CC
Laboratory for Pregnancy and Newborn Research, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Kalmar-Nagy
J
J
Engelen
M
M
Koenen
S V
SV
Nijland
M
M
Kuc
R E
RE
Davenport
A P
AP
Nathanielsz
P W
PW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000737:chemistry / Q000196:embryology / Q000502:physiology; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007457:Iodine Radioisotopes; D020768:Middle Cerebral Artery / Q000737:chemistry / Q000196:embryology / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000032:analysis / Q000378:metabolism; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D001381:Azepines; D019332:Endothelin-1; D005938:Glucocorticoids; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; C087850:PD 151242; D003907:Dexamethasone; D000109:Acetylcholine; D011188:Potassium