Document Detail


Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased uterine perfusion.
MedLine Citation:
PMID:  16391174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The initiating event in preeclampsia is thought be to reduced uteroplacental perfusion. Although we have reported previously that chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats results in hypertension and enhanced endothelin production, the factors linking placental ischemia and endothelial cell activation remain unclear. The purpose of this study was to determine the role of angiotensin II type-1 (AT1) receptor activation on endothelin production induced by serum from pregnant rats exposed to reductions in uterine perfusion. To achieve this goal, human umbilical vein endothelial cells were exposed to sera collected from RUPP rats or normal pregnant rats. Arterial pressure was significantly higher in RUPP rats (135+/-2 mm Hg) than in pregnant rats (106+/-1 mm Hg). Six hours after exposure to RUPP serum (n=17), cell media endothelin concentration was 18.4+/-2.7 pg/mL as compared with 9.22+/-1.3 pg/mL from cells exposed to serum from normal pregnant rats (n=9). Eighteen hours after exposure to RUPP serum (n=7), endothelin concentration was 30.5+/-3.8 pg/mL as compared with 12.8+/-5.3 pg/mL from cells exposed to normal pregnant rat serum (n=6). In contrast, serum from RUPP rats did not increase endothelin production in human umbilical vein endothelial cells pretreated with an AT1 receptor antagonist, losartan (15 micromol/L). Eighteen hours after exposure to RUPP serum and losartan (n=14), endothelin concentration was 21.3+/-2.2 pg/mL as compared with 16.4+/-3.3 pg/mL from cells exposed to normal pregnant rat serum and losartan (n=10). These data indicate that serum from pregnant rats exposed to reductions in uterine perfusion enhances endothelin production by endothelial cells via by AT1 receptor activation.
Authors:
Lyndsay Roberts; B Babbette D LaMarca; Lillian Fournier; Jennifer Bain; Kathy Cockrell; Joey P Granger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-01-03
Journal Detail:
Title:  Hypertension     Volume:  47     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-17     Completed Date:  2006-03-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  615-8     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II Type 1 Receptor Blockers / pharmacology
Animals
Cells, Cultured
Endothelial Cells / drug effects,  metabolism*
Endothelins / biosynthesis*,  metabolism
Female
Humans
Losartan / pharmacology
Osmolar Concentration
Pregnancy
Pregnancy, Animal / blood*
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 / metabolism*
Regional Blood Flow
Time Factors
Uterus / blood supply*
Grant Support
ID/Acronym/Agency:
HL38499/HL/NHLBI NIH HHS; HL51971/HL/NHLBI NIH HHS; HL66661/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Endothelins; 0/Receptor, Angiotensin, Type 1; 114798-26-4/Losartan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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