Document Detail


Attenuated PGI2 synthesis in obese Zucker rats.
MedLine Citation:
PMID:  19118096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In obesity, skeletal muscle blood flow during exercise (functional hyperemia) is impaired. We have indirectly demonstrated that an altered arachidonic acid metabolism is responsible for the impaired functional vasodilation in the obese Zucker rat (OZR), a model of obesity. In this study, we tested the hypothesis that there is an impaired release of PGI(2) due to a nitration of PGI(2) synthase (PGIS), which is associated with a decreased prostanoid receptor expression. PGI(2), PGE(2), and thromboxane A(2) (TXA(2)) release were determined in vitro using ELISA under basal conditions and in response to arachidonic acid (AA) administration (50 microM). Immunofluorescence of PGI(2) and TXA(2) receptors (IP and TP, respectively) was determined in dispersed vascular smooth muscle cells (VSMCs). Nitration of tyrosine residues of the PGIS enzyme was determined using immunoprecipitation and Western blot analysis. Following AA administration, PGI(2) and PGE(2) release were attenuated in OZR compared with lean Zucker rats (LZR; controls). Basal and AA-induced TXA(2) release were not significantly different between groups. IP and TP immunofluorescence were not significantly different between OZR and LZR groups. OZR exhibited elevated nitration of tyrosine residues of PGIS compared with LZR. These results suggest that alterations in the PGI(2) pathway (attenuated PGI(2) synthesis), and not the TXA(2) pathway (normal TXA(2) synthesis/no change in TP receptor expression), underlie the attenuated functional hyperemia in the OZR.
Authors:
Benjamin L Hodnett; Jennifer A Dearman; Cory B Carter; Robert L Hester
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-12-31
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  296     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-27     Completed Date:  2009-04-13     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R715-21     Citation Subset:  IM    
Affiliation:
Dept. of Physiology and Biophysics, Univ. of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acid / metabolism
Blotting, Western
Cell Separation
Epoprostenol / biosynthesis*
Fluorescent Antibody Technique
Male
Microcirculation / physiology
Myocytes, Smooth Muscle / metabolism
Nitrates / metabolism
Obesity / metabolism*
Physical Conditioning, Animal / physiology
Rats
Rats, Zucker
Receptors, Epoprostenol / biosynthesis
Receptors, Thromboxane A2, Prostaglandin H2 / biosynthesis
Tyrosine / metabolism
Grant Support
ID/Acronym/Agency:
HL-51971/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Nitrates; 0/Receptors, Epoprostenol; 0/Receptors, Thromboxane A2, Prostaglandin H2; 35121-78-9/Epoprostenol; 506-32-1/Arachidonic Acid; 55520-40-6/Tyrosine
Comments/Corrections

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


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