The challenge of pregnancy to the mother requires that her own metabolic and endocrine needs be met while
also taking on the literally growing demands of the unborn child. While all of the mother’s organs require continued support,
the uterus and now added placenta must also develop substantially. One critical area of adaptation is thus the ability
to provide added blood flow over and above that already serving the preexisting maternal organs. Previous reviews have
covered in detail how this is achieved from an endocrine or indeed vascular physiology standpoint and we will not repeat
that here. Suffice it to say in addition to new vessel growth, there is also the need to achieve reduced vascular resistance
through maintenance of endothelial vasodilation, particularly through NO and PGI2 production in response to multiple
agonists and their associated cell signaling systems. In this review, we continue our focus on pregnancy adaptive changes
at the level of cell signaling, with a particular emphasis now on the developing story of the critical role of gap junctions.
Remapping of cell signaling itself beyond changes in individual hormones and respective receptors brings about global
changes in cell function, and recent studies have revealed that such post-receptor changes in cell signaling are equally if
not more important in the process of pregnancy adaptation of endothelial function than the upregulated expression of
vasodilator synthetic pathways themselves. The principle significance, however, of reviewing this aspect of pregnancy adaptation
of endothelial cell function is that these same gap junction proteins that mediate pregnancy-adapted changes in
vasodilatory signaling function may also be the focal point of failure in diseased pregnancy, and clues as to how and why
are given by comparing studies of Cx43 functional suppression at wound sites with studies of preeclamptic pregnancy. If
preeclamptic pregnancy is indeed a pregnancy misconstrued by the body in endocrine terms to be a wound, then the
kinases so activated that correspondingly suppress Cx43 function in the vascular endothelium may also be valid pharmacologic
targets for novel therapies in the near future.
Keywords: Endothelial, nitric oxide, Ca2+, programming, connexin.
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