Evidence for microvascular dysfunction after prenatal dexamethasone at 0.7, 0.75, and 0.8 gestation in sheep.
Dexamethasone (DM) was administered to pregnant ewes as three weekly courses of four injections of 2 mg at 12-h intervals. DM (n = 7) or saline (n = 7) was given starting at 103 days of gestation (dGA; term approximately 149 days). Fetal femoral arteries (approximately 300-microm internal diameter) were evaluated using wire myography at 119 dGA. DM-exposed fetuses were significantly smaller than saline-exposed fetuses. DM exposure increased maximal contraction to 125 mM KCl, and maximum tension developed along with sensitivity to endothelin-1 and relaxation to bradykinin. Preincubation with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester shifted the dose-response curves to endothelin-1 and acetylcholine to the right in controls but not in the DM-exposed group. Relaxation to acetylcholine and to the nitric oxide donor sodium nitroprusside was similar in both groups. The combination of enhanced endothelin-induced vasoconstriction, abnormal endothelium-dependent relaxation, and normal endothelium-independent relaxation indicates microvessel dysfunction following antenatal DM administration. Because such dysfunction is associated with several forms of adult hypertension, our results indicate the potential for consequences of antenatal glucocorticoid exposure on adult cardiovascular health.
Edward Melby Cardiovascular Research Laboratory, Laboratory for Pregnancy and Newborn Research, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Judit
J
Molnar
Mark J M
MJ
Nijland
David C
DC
Howe
Peter W
PW
Nathanielsz
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000196:embryology; D008833:Microcirculation / Q000187:drug effects* / Q000196:embryology; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D003907:Dexamethasone; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester