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Articles in PresS, published online ahead of print May 15, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00031.2002
Submitted on January 22, 2002
Accepted on May 8, 2002
1 Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA
* To whom correspondence should be addressed. E-mail: pwn1{at}cornell.edu.
Dexamethasone (DM) was administered to pregnant ewes as three weekly courses of 4 injections of 2mg at 12h intervals. DM (n=7) or saline (n=7) were given starting at 103 days of gestation (dGA; term~149days). Fetal femoral arteries (~300µm internal diameter) were evaluated using wire myography at 119dGA. DM-exposed fetuses were significantly smaller than saline-exposed fetuses. DM-exposure increased maximal contraction to 125mM KCl, maximum tension developed and sensitivity to endothelin-1, and relaxation to bradykinin. Preincubation with the nitric oxide synthase inhibitor L-NAME 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. Since 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.
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