Central noradrenergic regulation of cerebral blood flow and vascular permeability.

TLDR

Central noradrenergic fibers are present on small intraparenchymal vessels, distinct from the peripheral system that innervates larger vessels. The study tests whether the central noradrenergic system functions like the peripheral sympathetic system but specifically regulates brain microvasculature. Cerebral blood flow and water permeability were measured in four adult rhesus monkeys, some with bilateral superior cervical ganglionectomies, using cannulae in the lateral ventricles and locus coeruleus to administer drugs. Stimulation of locus coeruleus with carbachol lowered hemispheric cerebral blood flow and increased water permeability, while the alpha‑adrenergic blocker phentolamine produced the opposite effect, supporting the hypothesis of central noradrenergic regulation of brain vascular permeability and flow.

Abstract

Anatomical studies employing the immunofluorescence localization of dopamine-beta-hydroxylase [= dopamine beta-monooxygenase; 3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating); EC 1.14.17.1] have demonstrated in brain central noradrenergic nerve fibers on small intraparenchymal blood vessels, including capillaries. This system is distinct from the peripheral noradrenergic system inervating the large extraparenchymal blood vessels. From these anatomical findings evolved the working hypothesis that the central noradrenergic system is analogous to the peripheral sympathetic system except that it is specialized for performing specific functions related to the brain microvasculature. To test this hypothesis cerebral blood flow and the brain vascular permeability of water (H215O) were measured in four adult rhesus monkeys (three with bilateral superior cervical ganglionectomies) with stereotaxically placed cannulae permanently located in the lateral ventricles and the locus coeruleus for the injection of drugs. Our data demonstrate that stimulation of the noradrenergic cell bodies in the locus coeruleus with carbachol (8 mug) produces a prompt reduction in hemispheric cerebral blood flow and an increase in brain vascular permeability of water. The intraventricular administration of the alpha-adrenergic blocker phentolamine (25--50 mug) has the opposite effect. These preliminary data support the hypothesis that the central noradrenergic system is analogous to the peripheral sympathetic system with the special function of regulating brain vascular permeability as well as blood flow.