Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression
- PMID: 12409963
- DOI: 10.1097/00004872-200211000-00024
Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression
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.
Comment in
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Endothelium-derived contracting factor: a new way of looking at endothelial function in obesity.J Hypertens. 2002 Nov;20(11):2147-9. doi: 10.1097/00004872-200211000-00011. J Hypertens. 2002. PMID: 12409950 Review. No abstract available.
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