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Antenatal betamethasone increases vascular reactivity to endothelin-1 by upregulation of CD38/cADPR signaling

Published online by Cambridge University Press:  10 January 2014

J.-H. Lee ,
J. Zhang ,
G. A. Massmann  and
J. P. Figueroa
J.-H. Lee
Affiliation:
Department of Obstetrics and Gynecology, Center for Research in Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Jeonju, South Korea
J. Zhang
Affiliation:
Department of Obstetrics and Gynecology, Center for Research in Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
G. A. Massmann
Affiliation:
Department of Obstetrics and Gynecology, Center for Research in Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
J. P. Figueroa*
Affiliation:
Department of Obstetrics and Gynecology, Center for Research in Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
*
*Address for correspondence: Jorge P. Figueroa, Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. (Email figueroa@wakehealth.edu)
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Abstract

Antenatal steroid administration is associated with hypertension in adult life; however, the mechanisms underlying this phenomenon are unclear. The aim of this study was to further characterize the effects of antenatal glucocorticoid exposure on the endothelin (ET-1) system, specifically to ascertain the role of the cyclic adenosine diphosphate ribose (cADPR)/ryanodine receptor pathway in the increased sensitivity to ET-1 observed in the offspring exposed to antenatal glucocorticoids. Pregnant sheep were randomly treated with betamethasone (Beta; 0.17 mg/kg) or vehicle at 80 and 81 days of gestation. In adults, we studied endothelium-denuded arterial segments of the brachial arteries. ET-1-induced vasoconstriction was significantly higher in the arteries from Beta sheep (F=3.5, P<0.05). Inhibition of ADP-ribosyl cyclase with 2-2'-dihydroxy-azobenzene significantly decreased the ET-1-induced contraction in Beta but not in vehicle-treated sheep. Nicotinamide attenuated ET-1 contraction in both, but it was significantly more pronounced in the Beta-treated sheep. No significant differences were observed following KCl-induced (6.25–75 mM) contraction. Nicotinamide (10 mM) significantly attenuated the KCl-induced vasoconstriction in both groups. In KCl (62.5 mM)-constricted arteries, the effect of nicotinamide (NIC) was significantly greater in the vehicle-treated sheep (50% relaxation v. 40% relaxation; t=2.2, P<0.05). In contrast, the sodium nitroprusside (SNP) relaxation was not statistically different. An additive effect was observed when NIC and SNP were used in combination and it was also more pronounced in vehicle-treated sheep. We conclude that the increased response to ET-1 is mediated by activation of the CD38/cADPR signaling pathway. Further studies are required to identify the effectors downstream from cADPR affected by exposure to antenatal steroids.

Keywords

animallarge animalsmolecular/cellular
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 5 , Issue 1 , February 2014 , pp. 56 - 62
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

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