title: Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression.
abstract: OBJECTIVE
  Vasoconstrictor prostanoids have been implicated in abnormal vasomotion in atherosclerosis and hypertension.
  
  
  METHODS
  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.
authors.affiliation: Medical Policlinic and Clinical Atherosclerosis Research Laboratory, Department of Internal Medicine, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Traupe
authors.forename: Matthias
authors.initials: M
authors.lastname: Lang
authors.forename: Winfried
authors.initials: W
authors.lastname: Goettsch
authors.forename: Klaus
authors.initials: K
authors.lastname: Münter
authors.forename: Henning
authors.initials: H
authors.lastname: Morawietz
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Vetter
authors.forename: Matthias
authors.initials: M
authors.lastname: Barton
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002339:Carotid Arteries / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism*; D016232:Endothelins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017482:Receptors, Thromboxane / Q000235:genetics*; D013930:Thromboxane-A Synthase / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D017482:Receptors, Thromboxane; D014665:Vasodilator Agents; D009599:Nitroprusside; D013930:Thromboxane-A Synthase; D000109:Acetylcholine