Role of endothelin‑1 and its receptors in cerebral vasospasm following subarachnoid hemorrhage

Mol Med Rep. 2018 Dec;18(6):5229-5236. doi: 10.3892/mmr.2018.9513. Epub 2018 Sep 27.

Abstract

Cerebral vasospasm (CVS) is a severe complication of subarachnoid hemorrhage (SAH), and endothelin‑1 (ET‑1) may be involved in its pathogenesis. The present study aimed to investigate the expression of ET‑1 in cerebrospinal fluid (CSF) in patients with SAH and to analyze rat arterial contractility and the expression levels of ET‑1 receptors in vitro. CSF samples were collected from 28 patients and the expression levels of ET‑1 were measured. Rat cerebral basilar arteries were isolated and incubated with hemorrhagic or clear CSF. Contractility, as well as ETA and ETB mRNA expression were measured. ET‑1 levels in CSF increased and reached a peak within the initial 5 days after SAH onset and then gradually subsided. After 12 or 24 h, the contraction of arteries incubated in hemorrhagic CSF was substantially stronger than those in clear CSF. The mRNA expression levels of endothelin receptor type A and B in arteries incubated in hemorrhagic CSF were significantly higher than those in clear CSF. ET‑1 and its receptors may be involved in the pathogenic mechanism of CVS following SAH. ET‑1 expression in CSF may be used as a marker in CVS and its receptors may provide novel therapeutic targets in CVS.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Computed Tomography Angiography
  • Disease Models, Animal
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Endothelin-1 / pharmacology
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptor, Endothelin A / genetics
  • Receptor, Endothelin A / metabolism*
  • Subarachnoid Hemorrhage / cerebrospinal fluid
  • Subarachnoid Hemorrhage / complications*
  • Subarachnoid Hemorrhage / diagnosis
  • Time Factors
  • Tomography, X-Ray Computed
  • Vasospasm, Intracranial / etiology*
  • Vasospasm, Intracranial / physiopathology*

Substances

  • Endothelin-1
  • RNA, Messenger
  • Receptor, Endothelin A