Xiang, Lusha, Jay S. Naik, Benjamin L. Hodnett, and Robert L. Hester. Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 290: R134 -R138, 2006. First published September 15, 2005 doi:10.1152/ajpregu.00295.2005.-These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR and 6 OZR) was measured after 2 min of muscle stimulation in the absence or presence of 1 M SQ-29548 (TP antagonist). Additionally, arteriolar diameter (6 for each group) was measured after application of iloprost (prostacyclin analog; 0.28, 2.8, and 28 M), arachidonic acid (10 M), and sodium nitroprusside (0.1, 1, and 10 M) in the absence or presence of 1 M SQ-29548. A 10 M concentration of adenosine was used to induce a maximal dilation. Basal diameters were not different between LZRs and OZRs. Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 M SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs. Vasodilatory responses to iloprost and sodium nitroprusside (1 and 10 M) were significantly reduced in OZR. Adenosine-mediated vasodilation was not different between groups. These results suggest that the impaired functional dilation in the OZR is due to an increased TP-mediated vasoconstriction and a decreased PGI2-induced vasodilation.obese Zucker rat; prostacyclin; thromboxane; vasoconstriction IT IS WELL ESTABLISHED THAT, during periods of increased skeletal muscle metabolism (such as during exercise), blood flow to the muscle increases (functional hyperemia) because of dilation of local arterioles (functional dilation), and this vasodilatory response is dependent, in some part, on endothelial function (22). However, in patients and animals with metabolic syndrome, endothelial dysfunction may occur early in the pathology of this syndrome (4), possibly contributing to the impaired functional hyperemia seen in metabolic syndrome. For example, patients with type 2 diabetes exhibit an impaired endothelial-dependent vasodilatory response to ACh and a significant impairment of the functional hyperemic response to leg cycle ergometer exercise (14). Our laboratory and others (8,32) have demonstrated that the obese Zucker rat (OZR), a model of metabolic syndrome, have both an attenuated functional and ACh-induced vasodilation in skeletal muscle arterioles. Although the mechanism(s) responsible for the impaired functional dilation remains unclear, these studies reveal a possible relationship between the endothelial dysfunction and the impaired functional vasodilation.The determination of the mechanism(s) responsible...