title: Effect of OS-0689, a novel SERM, on periarterial nerve function in tail arteries of ovariectomized rats.
abstract: OBJECTIVE
  We have previously shown that OS-0689 attenuates the rise in tail skin temperature of ovariectomized rats, which is believed to be relevant to human symptoms of hot flush. In this study, we elucidate the mechanism underlying the ameliorating effects of OS-0689 on elevated tail skin temperature.
  
  
  METHODS
  Female Sprague-Dawley rats were ovariectomized and orally treated with OS-0544 (1 mg/kg), OS-0689 (3 mg/kg; (+)-enantiomer of OS-0544) or 17beta-estradiol (3 mg/kg; E2) for 1 week. At 1, 3 or 6 weeks after ovariectomy, the vasoconstrictions and vasorelaxations induced by periarterial nerve stimulation (PNS), l-noradrenaline (NA), and rat calcitonin gene-related peptide (CGRP) in isolated tail arteries were compared between OVX and sham-operated rats.
  
  
  RESULTS
  Three weeks after ovariectomy, vasoconstrictions in response to PNS and NA in the arteries of OVX rats were markedly less than those in the arteries of sham-operated rats. However, at 1 and 6 weeks after ovariectomy the stimuli-induced vasoconstrictions in the arteries of OVX rats were greater than those of sham-operated rats. Moreover, NA reactivity was not attenuated in the mesenteric arteries at 3 weeks after ovariectomy. OS-0544, OS-0689 and E2 prevented the decrease in vasoconstrictions in the tail arteries. Vasorelaxations in response to PNS and rat CGRP were significantly greater in the arteries of OVX rats than in those of the sham-operated rats. OS-0689 inhibited the increase in vasorelaxation induced by both stimuli, whereas E2 had no effects.
  
  
  CONCLUSIONS
  Ovariectomy not only decreases adrenergic function but also enhances CGRPergic function in rats' tail arteries. OS-0689 improves both impairments and thereby improves on rat hot flush.
authors.affiliation: Pharmacology and Microbiology Research Laboratories, Dainippon Pharmaceutical Co., Ltd, Enoki-cho 33-94, Suita, Osaka 564-0053, Japan. hisao-minato@dainippon-pharm.co.jp
authors.forename: Hisao
authors.initials: H
authors.lastname: Minato
authors.forename: Akihisa
authors.initials: A
authors.lastname: Ikeno
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Watanabe
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Tsuji
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002979:Climacteric / Q000097:blood / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007189:Indans / Q000494:pharmacology*; D010052:Ovariectomy; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012881:Skin Temperature / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*; D013237:Stereoisomerism; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C478564:3-(4-(1- piperidinoethoxy)phenyl)spiro(indene- 1,1'-indane)-5,5'-diol; D007189:Indans; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; D013141:Spiro Compounds; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide