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J Physiol Volume 565, Number 1, 59-69, May 15, 2005 DOI: 10.1113/jphysiol.2004.082420
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Angiotensin II regulation of ovine fetoplacental artery endothelial functions: interactions with nitric oxide

Jing Zheng1, Ian M. Bird1,2, Dong-Bao Chen4 and Ronald R. Magness1,2,3

1 Departments of Obstetrics and Gynecology, Perinatal Research Laboratories
2 Pediatrics
3 Animal Sciences, University of Wisconsin, Madison, WI 53715, USA
4 Department of Reproductive Medicine, Division of Maternal-Fetal Medicine, University of California, San Diego, CA 92093, USA

During normal pregnancy, elevated angiotensin II (Ang II) concentrations in the maternal and fetal circulations are associated with dramatic increases in placental angiogenesis and blood flow. Much is known about a local renin–angiotensin system within the uteroplacental vasculature. However, the roles of Ang II in regulating fetoplacental vascular functions are less well defined. In the fetal placenta, the overall in vivo vasoconstrictor responses of the blood vessels to Ang II infusion is thought to be less than that in its maternal counterpart, even though infused Ang II induces vasoconstriction. Recent data from our laboratories suggest that Ang II stimulates cell proliferation and increases endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) in ovine fetoplacental artery endothelial cells. These data imply that elevations of the known vasoconstrictor Ang II in the fetal circulation may indeed play a role in the marked increases in fetoplacental angiogenesis and that Ang II-elevated endothelial NO production may partly attenuate Ang II-induced vasoconstriction on vascular smooth muscle. Together with both of these processes, the high levels of Ang II in the fetal circulation may serve to modulate overall fetoplacental vascular resistance. In this article, we review currently available data on the expression of Ang II receptors in the ovine fetal placenta with particular emphasis on the effects of Ang II on ovine fetoplacental endothelium. The potential cellular mechanisms underlying the regulation of Ang II on endothelial growth and vasodilator production are discussed.

(Received 30 December 2004; accepted after revision 17 March 2005; first published online 24 March 2005)
Corresponding author J. Zheng: Departments of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, 7E Meriter Hospital, 202 S Park Street, Madison, WI 53715, USA. Email: jzheng{at}wisc.edu




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