PGI2 synthesis is impaired in obese Zucker rats

Abstract

During exercise, endothelial cell synthesis of prostacyclin (PGI2) increases while thromboxane (TXA2) 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 PGI2 synthesis is impaired, whereas TXA2 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). PGI2 and TXA2 metabolite levels (Table) in the buffer were detected using ELISA. Basal levels of PGI2 and TXA2 were not different between groups. AA‐induced PGI2 synthesis was significantly impaired in the OZR. AA significantly increased TXA2 production only in the LZR. The impairment in AA‐induced PGI2 release in the OZR indicates a diminished ability of the endothelium to synthesize PGI2. As PGI2 is a known mediator of the vasodilatory response in skeletal muscle during exercise, these results suggest that an attenuated PGI2 synthesis without an elevation in TXA2 production may be a mechanism underlying the impaired functional hyperemia associated with obesity. Supported by HL‐51971 and AHA Predoctoral Fellowship.