Histamine receptors mediating vascular responses in brain

Gross, Paul Munn (1981) Histamine receptors mediating vascular responses in brain. PhD thesis, University of Glasgow.

Abstract

Several facts suggest that histamine may influence the function of cerebral blood vessels. 1) Histamine has important vascular effects in non-neural organs; 2) Cerebral microvessels and arteries contain receptors for histamine; 3) Enzyme systems in brain capillaries, particularly adenylate cyclase, are sensitive to histamine; 4) Cerebral perivascular mast cells store histamine; 5) A non-mast cell pool of histamine is located within cerebral vascular smooth muscle; 6) Hista- minergic nerves are present in brain, and may innervate blood vessels; and 7) Histamine may modulate noradrenergic nerve activity in cerebral vessels. In the studies that form the basis for this thesis, I have examined several aspects of brain vascular responses to histamine. These include an examination of blood-brain barrier permeability during carotid arterial infusion of histamine, cerebral blood flow responses to arterial infusion of histamine and its agonists, and responses of pial arterioles and veins to 1) perivascular injection of histamine agents, and 2) the interaction of noradrenergic and histaminergic stimuli. In the studies examining cerebrovascular peririeability (blood-brain barrier), histamine was infused into the internal carotid artery of anaesthetised rats, and quantitative measurements were made of vascular permeability to sucrose and a neutral amino acid, alpha-aminoisobutyric acid. Histamine increased permeability up to 237% in several brain regions (e.g., diencephalon, caudate nucleus, hippocampus, cerebral cortex) and in different areas of cerebral cortex (e.g., visual, parietal, frontal, olfactory). Additional studies indicated that the permeability increase was reversible: it had persisted for at least 30 minutes, but permeability had returned to normal within two hours. Pretreatment by intravenous injection with the histamine H? receptor antagonist, metiamide, blocked the increase in permeability, while antagonism at H? receptors with mepyramine was ineffective. Studies determining regional brain water content indicated that oedema in cortical grey matter occurred during histamine infusion. Measurements of cerebral blood flow in anaesthetised rats were made by the intracarotid 133Xenon clearance technique and also by tissue sampling to determine the brain distribution of tracer after systemic administration of labeled iodoantipyrine. Blood flow was measured before and after disruption of the blood-brain barrier by carotid injection of hypertonic urea. When the blood-brain barrier was intact, histamine had no effect on cerebral blood flow. After barrier opening, histamine increased blood flow in a concentration-dependent manner (26% to 50%). The participation of both histamine H1 and H2 receptors in mediating increases in blood flow was demonstrated by studies with the respective receptor antagonists during histamine infusion, and by carotid infusion of specific receptor agonists after blood-brain barrier opening. Dilatation of cerebral vessels during histamine infusion was not a secondary result to increased brain metabolism: histamine infusion after blood-brain barrier disruption did not produce detectable increases in cerebral glucose uptake. These results suggest that histamine acted on receptors within vascular smooth muscle to produce increases in blood flow. Pial arteriolar and venous responses to histamine and its pharmacological agonists were determined in anaesthetised cats by measuring vessel calibre before and after perivascular injection. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Neurosciences
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Harper, Murray
• Date of Award: 1981
• Depositing User: Enlighten Team
• Unique ID: glathesis:1981-72111
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 May 2019 12:58
• Last Modified: 15 Aug 2022 11:11
• Thesis DOI: 10.5525/gla.thesis.72111
• URI: https://theses.gla.ac.uk/id/eprint/72111