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

J Hypertens. 2002 Nov;20(11):2239-45. doi: 10.1097/00004872-200211000-00024.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Body Weight
  • Carotid Arteries / physiology
  • Endothelin-1 / metabolism*
  • Endothelins / genetics
  • Gene Expression / physiology
  • Hypertension / complications
  • Hypertension / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitroprusside / pharmacology
  • Obesity / complications
  • Obesity / physiopathology*
  • Protein Precursors / genetics
  • RNA, Messenger / analysis
  • Receptors, Thromboxane / genetics*
  • Thromboxane-A Synthase / genetics
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasodilator Agents / pharmacology


  • Endothelin-1
  • Endothelins
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Thromboxane
  • Vasodilator Agents
  • Nitroprusside
  • Thromboxane-A Synthase
  • Acetylcholine