Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression

Objectives Vasoconstrictor prostanoids have been implicated in abnormal vasomotion in atherosclerosis and hypertension. Method Using lean and diet-induced obese mice, we investigated whether obesity affects vascular function or expression of genes involved in prostanold action. Results In lean C57BL/6J mice, at high concentrations acetylcholine caused endothelium-dependent contractions in the carotid artery but not in the aorta. Endothelium-dependent contractions to acetylcholine were blocked by the non-selective cyclooxygenase (COX) inhibitors indomethacin and meclofenamate, or a prostaglandin H-2/thromboxane A(2) receptor antagonist, but not by inhibitors of COX-2, thromboxane synthase or cytochrome P-450 monooxygenase. Obesity increased endothelium-dependent contractions to acetylcholine in the carotid artery, and prostanoid-mediated vasoconstriction was now present in the aorta. Similarly, contractions to endothelin-1 were largely blocked by meclofenamate and were increased in the aorta of obese mice. Real-time quantitative polymerase chain reaction analysis of the thromboxane receptor gene in the carotid artery revealed a robust upregulation in obese animals (118-fold, P < 0.05); in comparison, obesity had a less pronounced effect on thromboxane synthase (2.1-fold increase, P < 0.05), or preproendothelin-1 gene expression (4.2-fold increase, P < 0.05).