title: Neuroprotective effects of selective β-1 adrenoceptor antagonists, landiolol and esmolol, on transient forebrain ischemia in rats; a dose-response study.
abstract: Although selective beta-1 adrenoceptor antagonists are known to provide neuroprotective effects after brain ischemia, dose-response relationships of their neuroprotective effects have not been examined. The present study was conducted to evaluate whether the degree of brain protection against transient forebrain ischemia would be influenced by different doses of selective beta-1 adrenoceptor antagonists, esmolol and landiolol, in rats. Adult male S.D. rats received intravenous infusion of saline 0.5 ml/h, esmolol 20, 200, 2,000 μg/kg/min, or landiolol 5, 50, 500 μg/kg/min. Infusion was initiated 30 min prior to ischemia and continued for 24h. Ten-minute forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries. Neurological and histological examinations were performed. Neurological deficit scores at 1, 4 and 7 days were lower, and the number of intact neurons in CA1 hippocampal region was larger in the rats treated with esmolol and landiolol after ischemia, compared with saline-treated rats (P<0.05), whereas no difference was found among different doses of esmolol and landiolol. These results suggested that selective beta-1 adrenoceptor antagonists improved neurological and histological outcomes following forebrain ischemia in rats, irrespective of their doses.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Japan. tgoyagi@doc.med.akita-u.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Goyagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Horiguchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Tobe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Masaki
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011412:Propanolamines / Q000627:therapeutic use*; D016548:Prosencephalon / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D009025:Morpholines; D018696:Neuroprotective Agents; D011412:Propanolamines; C077049:landiolol; D014508:Urea; C036604:esmolol