Dantrolene and nimodipine inhibits vasoconstriction of basilar artery in a rat subarachnoid hemorrhage model

Abstract

Cerebral vasoconstriction is associated with increased cytosolic Ca+2 concentration in vascular smooth muscle, presumably due to Ca+2influx and Ca+2release from intracellular stores. We have previously shown that dantrolene has synergistic effects with nimodipine against serotonin (5‐HT)‐induced vasoconstriction in rat isolated cerebral arteries. We aimed to investigate the effects of dantrolene and nimodipine in a rat subarachnoid hemorrhage (SAH) model. Using an infusion pump 400μl blood or saline was given with intracysternal injection to Sprague‐Dawley rats. After 48 hours brain was removed and basilar artery was isolated and mounted into a wire myograph. Vasoconstriction of basilar artery was measured while exposed to KCl and 5‐HT in the presence or absence of dantrolene (10, 100μM) and/or nimodipine (30μM). Compared to saline group, 5‐HT‐induced vasoconstriction increased in SAH. Dantrolene significantly inhibited the constriction to 5‐HT whereas it was not affected the constriction to KCl. Nimodipine inhibited both KCl and 5‐HT constrictions significantly. When given together with dantrolene, nimodipine did not show an additional inhibition in KCl and 5‐HT‐induced vasoconstrictor responses. Our results suggest that dantrolene and nimodipine inhibit 5‐HT‐induced vasoconstriction but they do not have a synergistic effect in basilar artery of a SAH model in rat.