title: Raloxifene improves vascular reactivity in pressurized septal coronary arteries of ovariectomized hamsters fed cholesterol diet.
abstract: Although vascular effects of selective estrogen receptor modulators (SERMs) have been extensively examined in conduit arteries, whether SERMs could favorably modulate myogenic response in resistance arteries is unknown. The impact of raloxifene therapy and cholesterol diet on myogenic constriction during estrogen deficiency is unresolved. This study investigated changes in vascular reactivity and myogenic responses in female ovariectomized (Ovx) hamsters fed high-cholesterol diet (HCD) with and without chronic treatment of raloxifene. Functional studies were performed on hamster septal coronary arteries cannulated in a pressure myograph. Acetylcholine (ACh)-induced dilatation was reduced in arteries from cholesterol-fed Ovx hamsters, but not in those from cholesterol-fed hamsters, while pressure-induced myogenic constriction was unaffected. Chronic treatment with raloxifene restored ACh-induced dilatation in cholesterol-fed Ovx hamsters. U46619-induced constriction was increased in arteries from cholesterol-fed Ovx hamsters but not from cholesterol-fed control hamsters, which was normalized by chronic raloxifene treatment. The pressure-diameter relationship is presented as normalized diameter versus intraluminal pressure, while the effect of ACh or U46619 is expressed as percentage of tone at 80 mm Hg. Two-way analysis of variance (ANOVA) followed by Bonferroni post-tests were used for statistical evaluation among different treatment groups. P<0.05 was taken as statistically significant. The present results show that chronic treatment with raloxifene could benefit myogenically active coronary arteries by (i) restoring ACh-induced dilatation and (ii) reducing U46619-induced constriction without affecting pressure-induced myogenic responses in cholesterol-fed hamsters during estrogen deficiency. If such benefit can be observed in humans, raloxifene and other SERMs may be useful to preserve endothelial function and curtail vascular hypersensitivity in resistance coronary arteries in post-menopausal women with hypercholesterolemia or hyperlipidemia, a lipid condition implicated in the pathogenesis of myocardial infarction.
authors: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, and School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China. yc_chan@alumni.cuhk.net
authors: Yau-Chi
authors: YC
authors: Chan
authors: Fung Ping
authors: FP
authors: Leung
authors: Xiao Yu
authors: XY
authors: Tian
authors: Lai Ming
authors: LM
authors: Yung
authors: Chi Wai
authors: CW
authors: Lau
authors: Zhen Yu
authors: ZY
authors: Chen
authors: Xiaoqiang
authors: X
authors: Yao
authors: Ismail
authors: I
authors: Laher
authors: Yu
authors: Y
authors: Huang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity; D008078:Cholesterol, LDL / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008049:Lipase / Q000097:blood; D008647:Mesocricetus; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010052:Ovariectomy / Q000379:methods; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D020849:Raloxifene Hydrochloride; D008049:Lipase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester