Raloxifene lowers ischaemia susceptibility by increasing nitric oxide generation in the heart of ovariectomized rats in vivo

European Journal of Pharmacology
János NemcsikImre Pávó

Abstract

We studied the effects of a 2-week period of oral raloxifene therapy on the cardiac level of nitric oxide (NO) and on the susceptibility to angina in ovariectomized rats. Ovariectomy decreased the activity of Ca2+-dependent nitric oxide synthase (NOS) in the left ventricle, an effect restored by raloxifene (0.2-5 mg kg(-1) day(-1)) or 17beta-oestradiol (0.3 mg kg(-1) day(-1)). Ovariectomy led to a significant ST segment depression after the injection of (1) ornithine-vasopressin (0.5 IU kg(-1), i.v.) or (2) epinephrine (10 microg kg(-1), i.v.), followed 30 s later by phentolamine (15 mg kg(-1), i.v.); both effects were reversed by raloxifene or 17beta-oestradiol treatment. Inhibition of nitric oxide synthase (with NG-nitro-L-arginine methyl ester [L-NAME]; 5 mg kg(-1), s.c.) augmented the ST segment depression in the ovariectomized rat and abolished the anti-ischaemic effect of 17beta-oestradiol or raloxifene. Thus, an oestrogen deficiency down-regulates the cardiac constitutive nitric oxide synthase, which increases the susceptibility of the heart to ishaemia because both actions can be blocked by exogenous administration of the natural oestrogen 17beta-oestradiol or the selective oestrogen-receptor modulator (SERM) raloxifene...Continue Reading

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Citations

Oct 25, 2007·Digestive Diseases and Sciences·Rauf Onur EkCigdem Yenisey
Apr 16, 2015·Oxidative Medicine and Cellular Longevity·Anikó PósaCsaba Varga
Jul 12, 2011·Vascular Pharmacology·Matthias R MeyerMatthias Barton
Jan 6, 2009·Internal Medicine Journal·C M ZubrinichM F Sutherland
Sep 16, 2006·Nihon rinsho. Japanese journal of clinical medicine·Masahiro Nozaki
Oct 29, 2013·Oxidative Medicine and Cellular Longevity·Anikó PósaCsaba Varga
Jun 13, 2015·Oxidative Medicine and Cellular Longevity·Anikó PósaCsaba Varga
Aug 19, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Chiara BolegoAndrea Cignarella

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