Premium
PGI 2 synthesis is impaired in obese Zucker rats
Author(s) -
Hodnett Benjamin L,
Dearman Jennifer A,
Carter Cory B,
Hester Robert L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1141.4
Subject(s) - endocrinology , medicine , vasodilation , prostacyclin , arachidonic acid , chemistry , metabolite , thromboxane , basal (medicine) , endothelium , vascular smooth muscle , smooth muscle , biochemistry , platelet , enzyme , insulin
During exercise, endothelial cell synthesis of prostacyclin (PGI 2 ) increases while thromboxane (TXA 2 ) levels decrease. One hypothesis for the altered functional hyperemia in obesity is a shift in the normal balance of these arachidonic acid (AA) metabolites, resulting in an attenuation of normal vasodilation. Thus, we hypothesize that in the obese Zucker rat (OZR) model of obesity, AA‐induced PGI 2 synthesis is impaired, whereas TXA 2 production is enhanced. Equal length (4‐mm) segments of femoral arteries were removed from 12 – 14 week old lean (LZR) ( n = 10) and OZR ( n = 7), placed in wells of a plate containing a buffer solution, and incubated for 7 hrs (1 hr equil./3 hrs basal/3 hrs 50 μM AA). PGI 2 and TXA 2 metabolite levels (Table) in the buffer were detected using ELISA. Basal levels of PGI 2 and TXA 2 were not different between groups. AA‐induced PGI 2 synthesis was significantly impaired in the OZR. AA significantly increased TXA 2 production only in the LZR. The impairment in AA‐induced PGI 2 release in the OZR indicates a diminished ability of the endothelium to synthesize PGI 2 . As PGI 2 is a known mediator of the vasodilatory response in skeletal muscle during exercise, these results suggest that an attenuated PGI 2 synthesis without an elevation in TXA 2 production may be a mechanism underlying the impaired functional hyperemia associated with obesity. Supported by HL‐51971 and AHA Predoctoral Fellowship.