Therapeutically relevant concentrations of raloxifene dilate pressurized rat resistance arteries via calcium-dependent endothelial nitric oxide synthase activation

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 30, Issue 5, 2010, Pages 992-999

  Chan, Yau Chi ^a,b   Leung, Fung Ping ^a,b   Wong, Wing Tak ^a,b   Tian, Xiao Yu ^b   Yung, Lai Ming ^a   Lau, Chi Wai ^a,b   Tsang, Suk Ying ^b   Yao, Xiaoqiang ^a,b   Chen, Zhen Yu ^a,b   Huang, Yu ^a,b  

^a Institute of Vascular Medicine   (Australia)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Endothelial nitric oxide synthase; Mesenteric artery; Myogenic tone; Raloxifene; Selective estrogen receptor modulator

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; APAMIN; CALCIUM; CHARYBDOTOXIN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; N [3 (AMINOMETHYL)BENZYL]ACETAMIDINE; N(G) NITROARGININE METHYL ESTER; RALOXIFENE; WORTMANNIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTERY CONSTRICTION; ARTERY DIAMETER; ARTERY DILATATION; ARTERY ENDOTHELIUM; ARTERY RESISTANCE; ARTICLE; CALCIUM TRANSPORT; CELL STIMULATION; CONTROLLED STUDY; DRUG EFFECT; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; EXTRACELLULAR CALCIUM; FEMALE; FLUORESCENCE IMAGING; MALE; MESENTERIC ARTERY; MICROCIRCULATION; MYOGRAPHY; NONHUMAN; PRIORITY JOURNAL; RAT; SEX DIFFERENCE;

ANDROSTADIENES; ANIMALS; APAMIN; BLOOD PRESSURE; CALCIUM SIGNALING; CHARYBDOTOXIN; CHROMONES; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME ACTIVATION; ENZYME INHIBITORS; ESTRADIOL; ESTROGEN ANTAGONISTS; FEMALE; MALE; MESENTERIC ARTERIES; MORPHOLINES; NG-NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; OVARIECTOMY; PHOSPHORYLATION; POTASSIUM CHANNEL BLOCKERS; PROTEIN KINASE INHIBITORS; RALOXIFENE; RATS; RATS, SPRAGUE-DAWLEY; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SEX FACTORS; TIME FACTORS; VASCULAR RESISTANCE; VASODILATION; VASODILATOR AGENTS;

EID: 77951454070     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.110.203935     Document Type: Article

References (27)

1. Barrett-Connor E, Grady D, Sashegyi A, Anderson PW, Cox DA, Hoszowski K, Rautaharju P, Harper KD. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA. 2002;287:847-857.
2. Wong CM, Yao X, Au CL, Tsang SY, Fung KP, Laher I, Vanhoutte PM, Huang Y. Raloxifene prevents endothelial dysfunction in aging ovariec-tomized female rats. Vascul Pharmacol. 2006;44:290-298.
3. Chan YC, Leung FP, Yao X, Lau CW, Vanhoutte PM, Huang Y. Raloxifene modulates pulmonary vascular reactivity in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 2007;49:355-361.
4. Tsang SY, Yao X, Essin K, Wong CM, Chan FL, Gollasch M, Huang Y. Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage-sensitive Ca2+ channels. Stroke. 2004;35:1709-1714.
5. Chan YC, Leung FP, Yao X, Lau CW, Vanhoutte PM, Huang Y. Raloxifene relaxes rat pulmonary arteries and veins: roles of gender, endothelium, and antagonism of Ca2 + influx. J Pharmacol Exp Ther. 2005;312:1266-1271.
6. Leung FP, Yao X, Lau CW, Ko WH, Lu L, Huang Y. Raloxifene relaxes rat intrarenal arteries by inhibiting Ca2+ influx. Am J Physiol Renal Physiol. 2005;289:F137-F144.
7. Leung HS, Seto SW, Kwan YW, Leung FP, Au AL, Yung LM, Yao X, Huang Y. Endothelium-independent relaxation to raloxifene in porcine coronary artery. Eur J Pharmacol. 2007;555:178-184.
8. Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, McNabb MA, Wenger NK. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355: 125-137. (Pubitemid 44050394)
9. Collins P, Mosca L, Geiger MJ, Grady D, Kornitzer M, Amewou-Atisso MG, Effron MB, Dowsett SA, Barrett-Connor E, Wenger NK. Effects of the selective estrogen receptor modulator raloxifene on coronary outcomes in the Raloxifene Use for the Heart trial: results of subgroup analyses by age and other factors. Circulation. 2009;119:922-930.
10. Huang A, Sun D, Koller A, Kaley G. Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO. Am J Physiol. 1997;272:H1804-H1809.
11. Geary GG, Krause DN, Duckles SP. Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries. Am J Physiol. 1998;275:H292-H300.
12. Dunn WR, Wellman GC, Bevan JA. Enhanced resistance artery sensitivity to agonists under isobaric compared with isometric conditions. Am J Physiol. 1994;266:H147-H155.
13. Leung FP, Yung LM, Leung HS, Au CL, Yao X, Vanhoutte PM, Laher I, Huang Y. Therapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitro. Br J Pharmacol. 2007;152:223-229.
14. Kublickiene K, Svedas E, Landgren BM, Crisby M, Nahar N, Nisell H, Poston L. Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators. J Clin Endocrinol Metab. 2005; 90:6113-6122.
15. Snyder KR, Sparano N, Malinowski JM. Raloxifene hydrochloride. Am J Health Syst Pharm. 2000;57:1669-1675.
16. Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet. 2003;42: 361-372.
17. Hercule HC, Schunck WH, Gross V, Seringer J, Leung FP, Weldon SM, da Costa Goncalves A, Huang Y, Luft FC, Gollasch M. Interaction between P450 eicosanoids and nitric oxide in the control of arterial tone in mice. Arterioscler Thromb Vasc Biol. 2009;29:54-60.
18. Nakashima Y, Toki Y, Fukami Y, Hibino M, Okumura K, Ito T. Role of K + channels in EDHF-dependent relaxation induced by acetylcholine in canine coronary artery. Heart Vessels. 1997;12:287-293.
19. Sendao Oliveira AP, Bendhack LM. Relaxation induced by acetylcholine involves endothelium-derived hyperpolarizing factor in 2-kidney 1-clip hypertensive rat carotid arteries. Pharmacology. 2004;72:231-239.
20. Simoncini T, Genazzani AR, Liao JK. Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene. Circulation. 2002;105:1368-1373.
21. Ogita H, Node K, Asanuma H, Sanada S, Kim J, Takashima S, Minamino T, Hori M, Kitakaze M. Raloxifene improves coronary perfusion, cardiac contractility, and myocardial metabolism in the ischemic heart: role of phosphatidylinositol 3-kinase/Akt pathway. J Cardiovasc Pharmacol. 2004;43:821-829.
22. Yu J, Eto M, Kozaki K, Akishita M, Okabe T, Ouchi Y. Raloxifene analogue LY117018 suppresses oxidative stress-induced endothelial cell apoptosis through activation of ERK1/2 signaling pathway. Eur J Pharmacol. 2008;589:32-36.
23. Moritz A, Radtke OA, Gust R, Glusa E, Pertz HH. Characterisation of the relaxant response to raloxifene in porcine coronary arteries. Eur J Pharmacol. 2006;545:153-160.
24. Simoncini T, Genazzani AR. Raloxifene acutely stimulates nitric oxide release from human endothelial cells via an activation of endothelial nitric oxide synthase. J Clin Endocrinol Metab. 2000;85:2966-2969.
25. Sharma PK, Thakur MK. Estrogen receptor alpha expression in mice kidney shows sex differences during aging. Biogerontology. 2004;5: 375-381.
26. Colacurci N, Fornaro F, Cobellis L, De Franciscis P, Torella M, Sepe E, Arciello A, Cacciapuoti F, Paolisso G, Manzella D. Raloxifene slows down the progression of intima-media thickness in postmenopausal women. Menopause. 2007;14:879-884.
27. Takahashi K, Mori-Abe A, Takata K, Ohta T, Kawagoe J, Tsutsumi S, Ohmichi M, Kurachi H. Raloxifene improves the ovariectomy-induced impairment in endothelium-dependent vasodilation. Menopause. 2007; 14:656-661.