Identification of β-adrenergic-sensitive adenylate cyclase in intracranial blood vessels

Abstract

THE regulation of cerebral blood flow and vascular permeability is important in such clinical conditions as stroke, arterial spasm, vascular headache (for example, migraine) and metabolic effects of seizures. Unfortunately, relatively little is known about the nervous control of cerebral circulation, particularly with regard to the nature of the hormone and neurotransmitter receptors present in cerebral vessels. An influence of the adrenergic nervous system has been suggested by histological studies showing that the blood vessels and branches of the circle of Willis receive innervation from the sympathetic chain1, and that the smaller, penetrating cerebral vessels (called microvessels) are surrounded by noradrenaline-containing fibres which seem to arise from brainstem nor adrenergic nuclei2,3. Although attempts to demonstrate β-adrenergic receptors in cerebral vascular tissue by cytochemical methods have been unsuccessful4, indirect evidence for the presence of such receptors is suggested by reports that adrenergic stimulation can alter cerebral blood flow and vascular permeability3,5, and that cate-cholamine agonists (such as isoprenaline and adrenaline) can dilate whole-artery preparations of cerebral vessels6. We now report the presence of a β-adrenergic-stimulated adenylate cyclase in both superficial and deep cerebral blood vessels. In addition to supplying direct biochemical evidence for the existence of β-adrenergic receptors in the cerebral vasculature, identification of this enzyme should facilitate the evaluation of the actions of pharmacological agents on cerebral blood flow and vascular permeability.