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Titolo:
Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma NO concentrations, endothelin-1levels, and endothelium-dependent vasodilation in postmenopausal women
Autore:
Saitta, A; Altavilla, D; Cucinotta, D; Morabito, N; Frisina, N; Corrado, F; DAnna, R; Lasco, A; Squadrito, G; Gaudio, A; Cancellieri, F; Arcoraci, V; Squadrito, F;
Indirizzi:
Univ Messina, Sch Med, Dept Internal Med, Messina, Italy Univ Messina Messina Italy , Sch Med, Dept Internal Med, Messina, Italy Univ Messina, Sch Med, Dept Obstet & Gynecol, Messina, Italy Univ MessinaMessina Italy h Med, Dept Obstet & Gynecol, Messina, Italy
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 9, volume: 21, anno: 2001,
pagine: 1512 - 1519
SICI:
1079-5642(200109)21:9<1512:RDPSOE>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORONARY HEART-DISEASE; FLOW-MEDIATED VASODILATION; NITRIC-OXIDE; CONTROLLED TRIAL; IN-VITRO; CARDIOVASCULAR-DISEASE; OVARIECTOMIZED RATS; VASOMOTOR FUNCTION; SERUM-CHOLESTEROL; LY139481 HCL;
Keywords:
raloxifene; hormone replacement therapy; nitric oxide; endothelin-1; endothelium;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Squadrito, F Univ Messina, Azienda Policlin Univ, Sch Med, Dept Expt Med &Pharmacol,Sect Pharmacol, Torre Biol 5 Piano,Via C Valeria Gazzi, I-98125 Messina, Italy Univ Messina Torre Biol 5 Piano,Via C Valeria Gazzi MessinaItaly I-98125
Citazione:
A. Saitta et al., "Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma NO concentrations, endothelin-1levels, and endothelium-dependent vasodilation in postmenopausal women", ART THROM V, 21(9), 2001, pp. 1512-1519

Abstract

The endothelium is thought to play an important role in the genesis of atherosclerosis, and several lines of evidence suggest that the effect of an intervention on endothelial function might predict its involvement in coronary disease progression and in the rate of cardiovascular events. Estrogen has direct effects on the blood vessel wall, indicating that vascular endothelium may play a key role in the cardiovascular protective effects of hormone replacement therapy (HRT). Raloxifene relaxes coronary arteries in vitroby an estrogen receptor-dependent and NO-dependent mechanism, thus suggesting that this selective estrogen receptor modulator could also have beneficial effects on endothelial function. This study compared the effects of HRTand raloxifene on NO products, endothelin-1 plasma levels, and endothelium-dependent vasodilatation in postmenopausal women. Healthy postmenopausal women (n=90) were enrolled in a double-blind, randomized, placebo-controlled, 6-month trial. Women were randomly assigned to receive continuous HRT (1 mg 17 beta -estradiol combined with 0.5 mg norethisterone acetate), raloxifene (60 mg/d), or placebo for 6 months. Flow-mediated endothelium-dependentvasodilation of the brachial artery, plasma NO concentrations, and endothelin levels were measured at baseline and after 6 months of therapy. The mean baseline level of NO breakdown products was 26.5 +/- 10.7 mu mol/L and increased to 36.3+/-11.4 mu mol/L after 6 months of treatment with raloxifene. The mean baseline plasma endothelin level was 17.3+/-8.9 pg/mL and decreased to 11.5+/-2.1 pg/mL after 6 months of treatment with the selective estrogen receptor modulator. The mean baseline ratio of NO (breakdown products)to endothelin was also significantly increased at the end of treatment with raloxifene. Postmenopausal women treated with HRT had similar changes in plasma nitrites/nitrates and endothelin levels as well as in the ratio of NO to endothelin. In contrast, these markers of endothelial function did notchange in the placebo-treated women. Flow-mediated endothelium-dependent vasodilation of the brachial artery was 8.3+/-2.1% at baseline and increasedto 12.3+/-2.1% after 6 months of treatment with raloxifene. HRT also caused a significant and similar increase in flow-mediated endothelium-dependentvasodilation. No change in flow-mediated vasodilation was observed in the participants treated with placebo. We conclude that raloxifene therapy and HRT influence endothelial function and improve flow-mediated endothelium-dependent vasodilation to a comparable extent in healthy postmenopausal womenat least after a 6-month treatment period. However, further investigation is warranted to enhance our understanding of the mechanisms of the effect of raloxifene on vascular function and to determine whether its effect on endothelial function may contribute to the reduction in cardiovascular-related morbidity and mortality.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 08:21:51