Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage

Neurosurgery. 1993 Oct;33(4):707-14; discussion 714-5. doi: 10.1227/00006123-199310000-00022.


The role of endothelium-related factors in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has gained interest since the discovery of endothelin-1 (ET-1). We have examined, before and after SAH, the responsiveness of the cerebrovascular bed of the goat to ET-1, the sources of Ca2+ in ET-1-induced responses, and the ability of the Ca2+ entry blocker nicardipine to counteract them. Before SAH, injection of ET-1 into the cerebral circulation increased cerebrovascular resistance, thereby producing dose-dependent reductions in cerebral blood flow (CBF), which were prevented by nicardipine. In isolated middle cerebral arteries, ET-1 induced concentration-dependent contractions, which were equally inhibited in Ca(2+)-free medium (without or with ethylene glycol tetraacetic acid) and by the Ca2+ entry blocker nicardipine. On the third day after SAH, CBF was reduced by 28% and cerebrovascular resistance increased by 39%. At the same time, both ET-1-induced reductions in CBF and the constricting effects of ET-1 in vitro were enhanced. The ability of nicardipine to increase CBF and to inhibit the effects of ET-1 was impaired as a result of reduced dependence of cerebral arteries on extracellular Ca2+. On the seventh day after SAH, CBF and cerebrovascular resistance returned to control values, and effects of ET-1 became normal. It is suggested that the hyperreactivity to ET-1 of the cerebrovascular bed induced by SAH could have a role in the development of vasospasm, which could reduce the vascular effects of Ca2+ entry blockers after SAH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Brain / blood supply*
  • Dose-Response Relationship, Drug
  • Endothelins / pharmacology*
  • Female
  • Goats
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Nicardipine / pharmacology*
  • Subarachnoid Hemorrhage / physiopathology*
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology


  • Endothelins
  • Nicardipine