Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

PLoS One

Maurizio Berardino¹  Luciana Mascia¹  Barbara Assenzio¹  Federica Civiletti¹  AnnaTeresa Mazzeo¹  Erica L. Martin¹  Ulf Simonsen²  Alessandro Ducati³  Marco Fontanella³  Riccardo Boccaletti³  Edgaras Stankevicius⁴ 

[1] Department of Anesthesia and Intensive Care, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy;Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, University of Aarhus, Aarhus, Denmark;Division of Neurosurgery, Department of Neuroscience, Azienda Ospedaliera Città della salute e della scienza di Torino, University of Turin, Turin, Italy;Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania

关键词: Cerebrospinal fluid;    Endothelium;    Cerebral arteries;    Smooth muscle cells;    Vasoconstriction;    Enzyme-linked immunoassays;    Endothelial cells;    Hemorrhage;   

DOI  :  10.1371/journal.pone.0116456

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Introduction 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.

【 授权许可】

CC BY