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Gap Junction Regulation of Vascular Tone: Implications of Modulatory Intercellular Communication During Gestation

Conference paper
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 814)

Abstract

In the vasculature, gap junctions (GJ) play a multifaceted role by serving as direct conduits for cell–cell intercellular communication via the facilitated diffusion of signaling molecules. GJs are essential for the control of gene expression and coordinated vascular development in addition to vascular function. The coupling of endothelial cells to each other, as well as with vascular smooth muscle cells via GJs, plays a relevant role in the control of vasomotor tone, tissue perfusion and arterial blood pressure. The regulation of cell-signaling is paramount to cardiovascular adaptations of pregnancy. Pregnancy requires highly developed cell-to-cell coupling, which is affected partly through the formation of intercellular GJs by Cx43, a gap junction protein, within adjacent cell membranes to help facilitate the increase of uterine blood flow (UBF) in order to ensure adequate perfusion for nutrient and oxygen delivery to the placenta and thus the fetus. One mode of communication that plays a critical role in regulating Cx43 is the release of endothelial-derived vasodilators such as prostacyclin (PGI2) and nitric oxide (NO) and their respective signaling mechanisms involving second messengers (cAMP and cGMP, respectively) that are likely to be important in maintaining UBF. Therefore, the assertion we present in this review is that GJs play an integral if not a central role in maintaining UBF by controlling rises in vasodilators (PGI2 and NO) via cyclic nucleotides. In this review, we discuss: (1) GJ structure and regulation; (2) second messenger regulation of GJ phosphorylation and formation; (3) pregnancy-induced changes in cell-signaling; and (4) the role of uterine arterial endothelial GJs during gestation. These topics integrate the current knowledge of this scientific field with interpretations and hypotheses regarding the vascular effects that are mediated by GJs and their relationship with vasodilatory vascular adaptations required for modulating the dramatic physiological rises in uteroplacental perfusion and blood flow observed during normal pregnancy.

Keywords

Connexins Nitric oxide Endothelium Cyclic nucleotides Vasodilation Uterine blood flow 
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Notes

Acknowledgements

Funding Sources: Supported by National Institutes of Health grants R25-GM083252 (BCA—ML Carnes, PI); and HL49210, HL87144, HD38843, and HL117341 (RRM, PI).

We wish to thank S. Omar Jobe, Mayra B. Pastore, Mary Y. Sun, Amanda Hankes, Rosalina Villalon Landeros, Jayanth Ramadoss, Jill M. Kock, Gladys E. Lopez, Terrance M. Phernetton, Jason L. Austin, Cindy Goss, and Tim Taylor for their assistance with these studies and manuscript preparation. This work was partial fulfillment of Bryan Ampey’s Ph.D. degree for the Endocrinology Reproductive Physiology Training Program.

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Perinatal Research Laboratories, Department of Obstetrics & Gynecology, School Medicine and Public HealthUniversity of Wisconsin – MadisonMadisonUSA
  2. 2.Fred Hutchinson Cancer Research CenterSeattleUSA
  3. 3.Department of Pediatrics, School Medicine and Public HealthUniversity of Wisconsin – MadisonMadisonUSA
  4. 4.Department of Animal Sciences, College of Agriculture and Life SciencesUniversity of Wisconsin – MadisonMadisonUSA

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