Neuroprotective effects of selective beta-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, 2000 μg/kg/min, or landiolol 5, 50, 500 μg/kg/min. Infusion was initiated 30 min prior to ischemia and continued for 24 h. 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