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Attenuated PGI2 synthesis in obese Zucker rats

By Benjamin L. Hodnett, Jennifer A. Dearman, Cory B. Carter and Robert L. Hester

Abstract

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 PGI2 due to a nitration of PGI2 synthase (PGIS), which is associated with a decreased prostanoid receptor expression. PGI2, PGE2, and thromboxane A2 (TXA2) release were determined in vitro using ELISA under basal conditions and in response to arachidonic acid (AA) administration (50 μM). Immunofluorescence of PGI2 and TXA2 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, PGI2 and PGE2 release were attenuated in OZR compared with lean Zucker rats (LZR; controls). Basal and AA-induced TXA2 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 PGI2 pathway (attenuated PGI2 synthesis), and not the TXA2 pathway (normal TXA2 synthesis/no change in TP receptor expression), underlie the attenuated functional hyperemia in the OZR

Topics: Appetite, Obesity, and Digestion
Publisher: American Physiological Society
OAI identifier: oai:pubmedcentral.nih.gov:2665840
Provided by: PubMed Central
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