Document Detail


eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling.
MedLine Citation:
PMID:  21555345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca(2+)](i) concentration in response to circulating hormones or physical forces. Herein, we discuss how pregnancy-specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca(2+)](i) signaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca(2+)](i) signaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase 'capacitative entry' [Ca(2+)](i) response, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca(2+)](i) signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy but may also apply to other common forms of hypertension.
Authors:
D S Boeldt; F X Yi; I M Bird
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2011-05-09
Journal Detail:
Title:  The Journal of endocrinology     Volume:  210     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-09     Completed Date:  2011-09-27     Revised Date:  2013-03-11    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  243-58     Citation Subset:  IM    
Affiliation:
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, WI 53715, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Animals
Calcium Signaling
Connexin 43 / physiology
Endothelium, Vascular / physiology
Enzyme Activation
Female
Humans
Models, Cardiovascular
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type III / metabolism*
Pre-Eclampsia / physiopathology
Pregnancy / physiology*
Signal Transduction
Tumor Necrosis Factor-alpha / physiology
Uterine Artery / physiology
Vascular Endothelial Growth Factor A / physiology
Grant Support
ID/Acronym/Agency:
HD38843/HD/NICHD NIH HHS; HL079020/HL/NHLBI NIH HHS; R01 HL079020/HL/NHLBI NIH HHS; R01 HL079020-06/HL/NHLBI NIH HHS; T32HD41921/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Connexin 43; 0/Tumor Necrosis Factor-alpha; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase Type III
Comments/Corrections
Comment In:
J Endocrinol. 2011 Sep;210(3):239-41   [PMID:  21824899 ]

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