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

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Traupe T, Lang M, Goettsch W, Munter K, Morawietz H, Vetter W, Barton M

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

J Hypertens. 2002 Nov;20(11):2239-45.

PubMed ID

12409963 [ View in PubMed

]

Abstract

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 prostanoid 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 H2/thromboxane A2 receptor antagonist, but not by inhibitors of COX-2, thromboxane synthase or cytochrome P450 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 (18-fold, 0.05); in comparison, obesity had a less pronounced effect on thromboxane synthase (2.1-fold increase, 0.05), or preproendothelin-1 gene expression (4.2-fold increase, 0.05). CONCLUSIONS: These data demonstrate that obesity augments prostanoid-dependent vasoconstriction and markedly increases vascular thromboxane receptor gene expression. These changes are likely to promote the development of vascular disease, hypertension and thrombosis associated with obesity.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Meclofenamic acid	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details