Docherty C C, Kalmar-Nagy J, Engelen M, Koenen S V, Nijland M, Kuc R E, Davenport A P, Nathanielsz P W
Laboratory for Pregnancy and Newborn Research, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Jul;281(1):R261-8. doi: 10.1152/ajpregu.2001.281.1.R261.
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.
在妊娠110 - 111天时，对植入仪器的胎羊静脉输注生理盐水或地塞米松（2.2微克·千克⁻¹·小时⁻¹，持续48小时）。测量胎羊血压发现，与对照组（n = 5）相比，地塞米松治疗组（n = 6）胎羊血压升高幅度更大（7.3±2.3 vs. 0.6±2.3 mmHg，P < 0.05）。通过剖宫产娩出胎羊，在氟烷麻醉下获取股肌和脑。使用线肌动描记法评估股动脉和大脑中动脉（内径约320微米）。地塞米松治疗组与对照组胎羊的股动脉和大脑中动脉对氯化钾（2.5 - 125 mM）的敏感性以及对125 mM钾离子最大血管收缩幅度相似。对照组和地塞米松治疗组胎羊股动脉对乙酰胆碱诱导的血管舒张作用相似。大脑中动脉对乙酰胆碱不舒张。地塞米松治疗组胎羊股动脉对内皮素-1（ET-1；0.1 pM - 0.1 μM）的敏感性以及ET-1诱导的血管收缩幅度大于对照组（P < 0.05）。用受体特异性配体进行的放射自显影研究表明，地塞米松治疗组胎羊股肌血管中主要受体亚型ET(A)受体结合增加（P < 0.001），而大脑中动脉中ET(A)受体结合减少（P < 0.01）。在所有检测组织中，ET(B)受体结合相对较少。我们得出结论，ET(A)受体结合增加导致对ET-1反应性增强，可能参与了地塞米松诱导的体内胎羊外周血管阻力增加。
