Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2.

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Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA

Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2.

J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5.

PubMed ID

12414874 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Diclofenac	Prostaglandin G/H synthase 1	Protein	Humans	Yes	Inhibitor	Details