Abstract | OBJECTIVE: DESIGN: Female mice (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery, mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7 micromol/kg), or placebo (n = 10-12/group). The biological effects of both treatments were assessed by measurements of bone mass and the degree of uterine atrophy. After 4 months of therapy, carotid artery thrombosis was induced by photochemical injury, and the time to vascular occlusion was measured. RESULTS: Both treatments increased bone mineral density (4.1%-7.85%). Reversal of macroscopic uterine atrophy was observed only in estrogen-treated mice. Ovariectomized mice had a shorter time to occlusion compared with sham-operated mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both estradiol and raloxifene significantly inhibited intra-arterial thrombosis in ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and 141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue were significantly increased by both raloxifene and estradiol with endothelial nitric oxide synthase expression being unaltered. Platelet adhesion (measured by surface coverage under a shear rate of 1,800 s for 2 min) was significantly reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and 10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively. CONCLUSIONS:
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Authors | Rami Abu-Fanne, Amnon Brzezinski, Mordechai Golomb, Etty Grad, A Joseph Foldes, Yoel Shufaro, David Varon, Alexander Brill, Chaim Lotan, Haim D Danenberg |
Journal | Menopause (New York, N.Y.)
(Menopause)
2008 Jan-Feb
Vol. 15
Issue 1
Pg. 98-104
ISSN: 1072-3714 [Print] United States |
PMID | 17549036
(Publication Type: Journal Article)
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Chemical References |
- Selective Estrogen Receptor Modulators
- Raloxifene Hydrochloride
- Estradiol
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type III
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Topics |
- Animals
- Arteries
(metabolism)
- Bone Density
(drug effects)
- Estradiol
(administration & dosage)
- Female
- Homeostasis
(drug effects)
- Menopause
(drug effects, metabolism)
- Mice
- Nitric Oxide Synthase
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Ovariectomy
- Platelet Adhesiveness
(drug effects)
- Raloxifene Hydrochloride
(administration & dosage)
- Selective Estrogen Receptor Modulators
(administration & dosage)
- Thrombosis
(metabolism, prevention & control)
- Treatment Outcome
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