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Cerebral Artery Vasoconstriction is Endothelin-1 Dependent Requiring Neurogenic and Adrenergic Crosstalk

[ Vol. 14 , Issue. 4 ]

Author(s):

Roel H.L. Haeren*, Sieuwke A. Hartmans, Jo De Mey, Govert Hoogland, Jim Dings, Olaf E.M.G. Schijns, Sander M.J. van Kuijk, Kim Rijkers, Paul Schiffers and Koo J. van Overbeeke   Pages 306 - 315 ( 10 )

Abstract:


Background: The regulation of cerebral arterial vasomotor tone involves several mechanisms. The role of sympathetic nerves and the adrenergic neurotransmitter, noradrenaline (NA), has been the subject of debate for decades. Moreover, the specific role of endothelin-1 (ET-1) in cerebral arterial vasoconstriction has not been elucidated to date. In this study, we evaluated the contribution of NA and ET-1 to cerebral artery vasoconstriction.

Methods: Arterial responses of rat middle cerebral arteries, and human pial cerebral arteries to cumulative concentrations of NA and ET-1, and to Electrical Field Stimulation (EFS), were evaluated. To assess the role of NA and ET-1 when EFS was applied, experiments were performed in the presence of adrenergic, neurogenic, and endothelin-1 receptor modulators.

Results: We found that vasoconstriction of cerebral arteries following EFS requires the application of exogenous NA, whereas neither EFS nor NA alone induced vasoconstriction. The observed vasoconstriction was abolished by α-adrenoreceptor antagonist, catecholamine-release inhibitor, blockade of the perivascular neurons, and by the endothelin-2 receptor antagonist (BQ123).

Conclusion: Based on our results, cerebral artery vasoconstriction requires simultaneous neurogenic and adrenergic activation and is ET-1 dependent. We hypothesize that NA modulates the release of ET-1. Upon release, ET-1 binds to the ETA-receptor on smooth muscle cells inducing cerebral artery vasoconstriction.

Keywords:

Cerebral artery, endothelin-1, human, noradrenaline, vasoconstriction, electrical field stimulation.

Affiliation:

Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Department of Neurosurgery, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht



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