Endothelial function and menopause: effects of raloxifene administration.
Postmenopausal women have more severe endothelial dysfunction than premenopausal women. In the present study, we evaluated the possible beneficial effect of raloxifene administration, a selective estrogen receptor modulator, on endothelial regulation in postmenopausal women. In a double-blind, randomized vs. placebo trial, 60 healthy postmenopausal women were treated with raloxifene (60 mg/d) or placebo for 4 months to evaluate the effect of raloxifene treatment on endothelial function. Furthermore, in raloxifene-treated subjects (n = 30), the effect of raloxifene was also assessed during the intraarterial infusion of N(G)-monomethyl-L-arginine (4 micromol/min). Raloxifene administration vs. placebo was associated with a decrease in plasma low-density lipoprotein cholesterol (P < 0.01), triglyceride (P < 0.05), thiobarbituric acid-reactive substance (P < 0.01), vascular cell adhesion molecule-1 (P < 0.05), intercellular adhesion molecule-1 (P < 0.001), and E-selectin (P < 0.001) levels and with an increase in plasma Trolox equivalent antioxidant capacity (P < 0.001) levels. Indeed, raloxifene treatment was also associated with a significant improvement in endothelial-dependent vasodilatation assessed by brachial reactivity technique. Raloxifene administration had no impact on endothelial-independent vasodilatation. Furthermore, intraarterial infusion of N(G)-monomethyl-L-arginine inhibited the significant effect of raloxifene on endothelium-mediated brachial arterial diameter and flow. In conclusion, our results demonstrate that raloxifene administration is associated with a positive modulation of endothelial-dependent vasodilatation likely due to a reduction of risk factors for endothelial damage.
Colacurci
Nicola
N
Department of Gynecology and Obstetrics, Second University of Naples, I-80138 Naples, Italy.
Manzella
Daniela
D
Fornaro
Felice
F
Carbonella
Marco
M
Paolisso
Giuseppe
G
D000328:Adult; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008078:Cholesterol, LDL / Q000097:blood; D002839:Chromans / Q000097:blood; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008593:Menopause / Q000502:physiology*; D010919:Placebos; D017698:Postmenopause; D017697:Premenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008078:Cholesterol, LDL; D002839:Chromans; D019040:E-Selectin; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019323:omega-N-Methylarginine; D020849:Raloxifene Hydrochloride; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid