Adrenergic control of cerebral blood flow and energy metabolism in the rat.

Abstract

EVIDENCE NOW EXISTS that there are at least 2 types of adrenergic innervation of cerebral vessels, one from the cervical sympathetic plexus innervating mainly extracerebral arteries, but also reaching cerebral arterioles of 15 n diameter 1 ' 2 and the other originating in the locus ceruleus and impinging directly on the walls of intramedullary arterioles. 36The influences of these vascular neurogenic systems on cerebral circulatory physiology or metabolism are still not understood.Results of recent physiologic studies of the cerebral sympathetic system have been inconsistent, 7 " 10 probably reflecting the variety of animal models and methodology. There is evidence, however, that the sympathetic innervation of cerebral vessels influences vascular reactivity to changes in Paco 2 and Pao 2 and in some way functions to help maintain autoregulation. 1113 Harper recently proposed that the sympathetic nervous system is the coarse adjuster of cerebral blood flow (CBF), as contrasted to the fine control exerted by tissue metabolism. 14 The concept that mechanisms intrinsic to the brainstem, and probably neurogenic in character, are capable of influencing CBF and cerebral metabolic rate is supported by a variety of studies. Pial and cortical flow, as well as cerebral metabolism, may be increased by electrical stimulation of many areas in the brainstem siveness of cerebral vessels to CO 2 . 21 It has been suggested that these phenomena have a neurogenic origin, mediated by intramedullary neurons whose axons exit the brainstem in the fifth or seventh cranial nerves and eventually innervate cortical arteries. 23- 24 The recent discovery by immunofluorescence studies of an intramedullary adrenergic system speaks for direct neuronal action on parenchymal vessels as one basis for intrinsic control of CBF and metabolism. -*•2S The present experiments were designed to separate and define the roles of the intrinsic and extrinsic cerebral adrenergic neurons in the control of CBF and cerebral energy metabolism. Extrinsic adrenergic neurons are concerned with cerebral vascular autoregulation; the intrinsic (parenchymal) adrenergic system is essential to the metabolic regulation of CBF. MethodsStudies were performed on groups of male Wistar rats weighing between 250 and 350 grams and were designed to examine the effects of unilateral cervical sympathetic denervation on homolateral CBF and vascular resistance and the effects of certain drugs which alter both central and peripheral neuronal monoamine metabolism (reserpine) or block specific actions of monoamines on alpha and beta receptors of cerebral neurons and blood vessels (phenoxybenzamine, propranolol). In order to accomplish this, it was necessary to devise a system of internal controls to minimize the variables. Two major groups of animals were studied: one received no drugs and the other received reserpine, phenoxybenzamine, or propranolol. The animals in group 1 were divided into

Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism

“…1 h before the assay) reduced the calculated rate of high energy use by ~ 50% based on postmortem changes in rat brain energy metabolite levels, whereas the non‐specific α‐blocker, phenoxybenzamine had no effect (Kogure et al . ). A still‐lower propranolol dose (2.5 mg/kg, i.v.)…”

The metabolic trinity, glucose–glycogen–lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression

“…Astrocytes are known targets of the locus coeruleus, and they have ␣ 1 -, ␣ 2 -, ␤ 1 -and ␤ 2 -adrenergic receptors linked to different second messenger and signaling pathways that modulate their glucose transport, glycolysis, oxidative metabolism, glycogen synthesis and degradation, glutamate uptake, glutamine hydrolysis, and other activities; in general, these processes are stimulated in cultured astrocytes by receptor agonists, with the specific effects dependent on receptor subtypes and signaling pathways [29,32,33,50,51]. Noradrenergic pathway intervention can cause either a rise or fall in brain glucose utilization in animals, depending on condition (with or without stimulation), brain region, and the agonists or antagonists used to target adrenoceptor subtypes [36,38,40,59,60]. Stimulation of glycogenolysis by noradrenaline has a profound effect because even a severe energy crisis does not overwhelm its regulatory contributions; during ischemia and seizures more glycogen remains in the ipsilateral cerebral cortex after unilateral lesion of the locus coeruleus [27,35].…”

Anesthetics Affect the Cerebral Metabolic Response to Circulatory Catecholamines

“…In regard to CMRo,, it has been suggested that catecholamines increase CMRo, by direct stimulation of metabolism as is seen in peripheral tissue (Himms-Hagen, 1967). Kogure et al (1979) reported that administration of reserpine (to deplete central monoamines) or propanolol (to block central p receptors) reduced the rate of high-energy phosphate depletion following decapitation in cervical sympathetic ganglionectomized rats whereas denervation alone had no effect. These results were interpreted to suggest that central adrenergic neurons influence CMRo, by acting on p receptor sites on the cell membrane.…”