Cyclooxygenase-2-derived prostaglandin F2alpha mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging

Circ Res. 2009 Jan 30;104(2):228-35. doi: 10.1161/CIRCRESAHA.108.179770. Epub 2008 Dec 18.


Hypertension and vascular dysfunction result in the increased release of endothelium-derived contracting factors (EDCFs), whose identity is poorly defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can generate EDCFs and identified the possible EDCF candidate. Changes in isometric tension of aortae of young and aged hamsters were recorded on myograph. Real-time changes in intracellular calcium concentrations ([Ca(2+)](i)) in native aortic endothelial cells were measured by imaging. Endothelium-dependent contractions were triggered by acetylcholine (ACh) after inhibition of nitric oxide production and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane-prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises in endothelial cell [Ca(2+)](i). RT-PCR and Western blotting showed COX-2 expression mainly in the endothelium. Enzyme immunoassay and high-performance liquid chromatography-coupled mass spectrometry showed release of prostaglandin (PG)F(2alpha) and prostacyclin (PGI(2)) increased by ACh; only PGF(2alpha) caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF(2alpha) were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane-prostanoid receptor-mediated ACh- or PGF(2alpha)-induced contractions and COX-2-dependent release of PGF(2alpha). The present study demonstrates that PGF(2alpha), derived from COX-2, which is localized primarily in the endothelium, is the most likely EDCF underlying endothelium-dependent, thromboxane-prostanoid receptor-mediated contractions to ACh in hamster aortae. These contractions involved increases in endothelial cell [Ca(2+)](i). The results support a critical role of COX-2 in endothelium-dependent contractions in this species with an increased importance during aging and, possibly, a similar relevance in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Age Factors
  • Aged
  • Aging / metabolism*
  • Animals
  • Aorta / drug effects
  • Aorta / enzymology*
  • Calcium / metabolism
  • Cricetinae
  • Cyclooxygenase 2 / metabolism*
  • Dinoprost / metabolism*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Humans
  • Middle Aged
  • Reactive Oxygen Species / metabolism
  • Receptors, Thromboxane / metabolism
  • Renal Artery / enzymology
  • Signal Transduction
  • Vasoconstriction* / drug effects
  • Vasoconstrictor Agents / pharmacology


  • Reactive Oxygen Species
  • Receptors, Thromboxane
  • Vasoconstrictor Agents
  • Dinoprost
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Acetylcholine
  • Calcium