Inhibition of cerebral vasoconstriction by dantrolene and nimodipine

Neurocrit Care. 2009;10(1):93-102. doi: 10.1007/s12028-008-9153-0. Epub 2008 Oct 16.


Introduction: Cerebral vasoconstriction is associated with increased cytosolic Ca(2+) concentration in vascular smooth muscle, presumably due to Ca(2+) influx and Ca(2+) release from intracellular stores. We tested the hypothesis that dantrolene (a blocker of Ca(2+)-induced Ca(2+) release from the ryanodine receptor channel on the sarco-endoplasmic reticulum) would potentiate the action of nimodipine (a voltage-dependent L-type Ca(2+) channel blocker, considered standard therapy for SAH) in inhibiting the vasoconstriction of isolated cerebral arteries.

Method: Sprague-Dawley rat basilar and femoral arteries were analyzed for ryanodine receptor expression by immunofluorescence and PCR. Vasoconstriction of basilar artery ex vivo was measured in a wire myograph while exposed to serotonin (5-HT) or endothelin-1 (ET-1) in the presence or absence of dantrolene (10-100 muM) and/or nimodipine (30 nM). Femoral artery was examined for comparison.

Results: Basilar and femoral arteries express only the ryanodine receptor 3 (RyR3) isoform. In both basilar and femoral arteries, dantrolene significantly inhibited the constriction to 5-HT, whereas it poorly affected the constriction to ET-1. The inhibitory effect of dantrolene on 5-HT was substantially increased by nimodipine, inducing a 10-fold increase in the 50% effective concentration of 5-HT and a 46% reduction in maximum basilar constriction. In femoral artery, dantrolene modestly affected constriction to phenylephrine and there was no interaction with nimodipine.

Conclusion: Dantrolene has synergistic effects with nimodipine against 5-HT-induced vasoconstriction in isolated cerebral arteries. Dantrolene-nimodipine interaction will require testing in a pathophysiological model but might provide treatment for reducing SAH-related vasospasm or other 5-HT-related vasospastic syndromes, such as Call-Fleming syndrome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basilar Artery / drug effects*
  • Basilar Artery / physiology
  • Dantrolene / pharmacology*
  • Femoral Artery / drug effects
  • Femoral Artery / physiology
  • Male
  • Muscle Relaxants, Central / pharmacology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Nimodipine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Tissue Culture Techniques
  • Vasoconstriction / drug effects*
  • Vasodilator Agents / pharmacology*


  • Muscle Relaxants, Central
  • Ryanodine Receptor Calcium Release Channel
  • Vasodilator Agents
  • Nimodipine
  • Dantrolene