title: Cerebrospinal fluid from patients with subarachnoid haemorrhage and vasospasm enhances endothelin contraction in rat cerebral arteries.
abstract: BACKGROUND
  Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors.
  
  
  METHODS
  Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured.
  
  
  RESULTS
  Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed.
  
  
  CONCLUSIONS
  Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients with SAH.
authors: Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Barbara
authors: B
authors: Assenzio
authors: Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Erica L
authors: EL
authors: Martin
authors: Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Edgaras
authors: E
authors: Stankevicius
authors: Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Federica
authors: F
authors: Civiletti
authors: Division of Neurosurgery, Department of Neuroscience, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Marco
authors: M
authors: Fontanella
authors: Division of Neurosurgery, Department of Neuroscience, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Riccardo
authors: R
authors: Boccaletti
authors: Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Maurizio
authors: M
authors: Berardino
authors: Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: AnnaTeresa
authors: A
authors: Mazzeo
authors: Division of Neurosurgery, Department of Neuroscience, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Alessandro
authors: A
authors: Ducati
authors: Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, University of Aarhus, Aarhus, Denmark.
authors: Ulf
authors: U
authors: Simonsen
authors: Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy.
authors: Luciana
authors: L
authors: Mascia
mesh_terms: D000368:Aged; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism*; D002555:Cerebrospinal Fluid; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D017466:Receptors, Endothelin
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