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.