title: Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2.
abstract: Estrogens influence cardiovascular function through direct and indirect effects and via genomic and nongenomic mechanisms. The pathways underlying the nongenomic mechanisms are not completely understood. Estrogen-induced responses in vascular cells have been shown to influence prostaglandins and cyclooxygenase (COX), a key enzyme in the production of prostaglandins, with two isoforms, COX-1 and COX-2. We investigated the effects of prostaglandins on the acute potentiation by 17beta-estradiol (E) of acetylcholine (ACh)-mediated vasodilation in the cutaneous vasculature. Using a double-blind placebo-controlled design, we assessed skin blood flow in 32 healthy, postmenopausal women by laser Doppler velocimetry with direct current iontophoresis of ACh and sodium nitroprusside before and after 6-wk treatment periods with aspirin (a nonspecific COX-1 and COX-2 inhibitor), diclofenac (predominantly a COX-2 inhibitor, which also inhibits COX-1), celecoxib (a specific COX-2 inhibitor), given at anti-inflammatory doses, or placebo. Blood flux values before iontophoresis of ACh did not differ between the treatment groups or after E administration, excluding a direct cutaneous vasodilator effect of the treatments or of E. Acute E administration enhanced the response to ACh after aspirin, diclofenac, and placebo; however, this effect was completely abolished with celecoxib treatment (P < 0.05). E had no effect on sodium nitroprusside-mediated vasodilation after any of the treatments. We conclude that the COX-2 pathway plays a specific role in the rapid E-induced potentiation of cholinergic vasodilation in postmenopausal women.
authors.affiliation: Baker Medical Research Institute, St. Kilda Central, Melbourne 8008, Australia.
authors.forename: A C
authors.initials: AC
authors.lastname: Calkin
authors.forename: K
authors.initials: K
authors.lastname: Sudhir
authors.forename: S
authors.initials: S
authors.lastname: Honisett
authors.forename: M R I
authors.initials: MR
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Dawood
authors.forename: P A
authors.initials: PA
authors.lastname: Komesaroff
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage; D015992:Body Mass Index; D000068579:Celecoxib; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage; D004311:Double-Blind Method; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D017078:Laser-Doppler Flowmetry; D008565:Membrane Proteins; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D008076:Cholesterol, HDL; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D014280:Triglycerides; D004008:Diclofenac; D004958:Estradiol; D002784:Cholesterol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D000109:Acetylcholine; D001241:Aspirin