Document Detail


Maternal vasodilation in pregnancy: the emerging role of relaxin.
MedLine Citation:
PMID:  21613576     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pregnancy is a unique physiological condition of profound maternal renal and systemic vasodilation. Our goal has been to unveil the reproductive hormones mediating this remarkable vasodilatory state and the underlying molecular mechanisms. In addition to advancing our knowledge of pregnancy physiology, reaching this goal may translate into therapeutics for pregnancy pathologies such as preeclampsia and for diseases associated with vasoconstriction and arterial stiffness in nonpregnant women and men. An emerging player is the 6 kDa corpus luteal hormone relaxin, which circulates during pregnancy. Relaxin administration to rats and humans induces systemic and renal vasodilation regardless of sex, thus mimicking the pregnant condition. Immunoneutralization or elimination of the source of circulating relaxin prevents renal and systemic vasodilation in midterm pregnant rats. Infertile women who become pregnant by donor eggs (IVF with embryo transfer) lack a corpus luteum and circulating relaxin, and they show a markedly subdued gestational increase in glomerular filtration rate. These data implicate relaxin as one of the vasodilatory reproductive hormones of pregnancy. There are different molecular mechanisms underlying the so-called rapid and sustained vasodilatory actions of relaxin. The former is mediated by Gα(i/o) protein coupling to phosphatidylinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of endothelial nitric oxide synthase, the latter by vascular endothelial and placental growth factors, and increases in arterial gelatinase(s) activity. The gelatinases, in turn, hydrolyze big endothelin (ET) at a gly-leu bond to form ET(1-32), which activates the endothelial ET(B) receptor/nitric oxide vasodilatory pathway.
Authors:
Kirk P Conrad
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2011-05-25
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  301     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-03     Completed Date:  2011-10-18     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R267-75     Citation Subset:  IM    
Affiliation:
Department of Physiology and Functional Genomics, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida 32610, USA. kpconrad@ufl.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Humans
Male
Pregnancy
Relaxin / blood,  pharmacology*
Vasodilation / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
K11-HD-00662/HD/NICHD NIH HHS; R01-DK-063321/DK/NIDDK NIH HHS; R01-HD-030325/HD/NICHD NIH HHS; R01-HL-067937/HL/NHLBI NIH HHS; R21-HL-093334/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
9002-69-1/Relaxin
Comments/Corrections

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