The statins fluvastatin and pravastatin exert anti-flushing effects by improving vasomotor dysfunction through nitric oxide-mediated mechanisms in ovariectomized animals.
Statins have pleiotropic vascular protective effects that are independent of their cholesterol-lowering effects. The aim of the present study was to determine if statins have anti-flushing actions in an animal model of forced exercise-induced temperature dysregulation in menopausal hot flushes, and to clarify the critical role of statins in regulating vascular reactivity in the tail arteries of ovariectomized rats. Administration of fluvastatin or pravastatin (3mg/kg/day for 7days, p.o.) significantly ameliorated the flushing of tail skin in ovariectomized mice, and the effect of each statin was comparable with that of estrogen replacement (1mg/kg/week for 3weeks, i.m.). In phenylephrine-pre-contracted rat-tail arteries, ovariectomy inhibited acetylcholine-induced relaxation, but augmented sodium nitroprusside-induced relaxation. These ovariectomy-altered vasodilator responses were restored by fluvastatin treatment as well as by estrogen replacement. Nitrite/nitrate levels in the plasma of ovariectomized animals showed significantly lower values than those in sham-operated animals; this ovariectomy-reduced production of nitric oxide was improved by fluvastatin treatment. These data provide the first experimental evidence that statins such as fluvastatin and pravastatin exert anti-flushing effects by improving vasomotor dysfunction through nitric oxide-mediated mechanisms in ovariectomized animals. Thus, therapeutic methods that target improvement of vasomotor dysfunction could be novel strategies for reducing menopausal hot flushes.
Department of Pharmaceutical Care and Health Sciences, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan. shuto@fukuoka-u.ac.jp
Hideki
H
Shuto
Koji
K
Tominaga
Atsushi
A
Yamauchi
Munehiko
M
Ikeda
Kenji
K
Kusaba
Daisuke
D
Mitsunaga
Yasutoshi
Y
Hirabara
Takashi
T
Egawa
Yukio
Y
Takano
Yasufumi
Y
Kataoka
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D015914:Estrogen Replacement Therapy; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D019584:Hot Flashes / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008593:Menopause / Q000097:blood / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010805:Physical Conditioning, Animal / Q000009:adverse effects; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D012867:Skin / Q000098:blood supply; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*
D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D009569:Nitric Oxide; D000077340:Fluvastatin; D017035:Pravastatin