Abstract
Receptor sites for neurotransmitters may be spatially oriented within cerebral vascular walls. The direction from which neurohumoral stimuli arise (e.g., perivascular or intravascular) and the location and type of receptor activated may therefore determine the nature of vascular response. I review a series of studies that examined cerebrovascular responses to histamine and suggest that histamine receptors are differentially and spatially organized in two profiles within the cerebral circulation. A transmural distribution is suggested from the following results: increases in permeability of the blood-brain barrier (endothelial cells) to intra-arterial infusion of histamine were mediated by H2-receptors; increases in blood flow to intra-arterial infusion of histamine occurred only after the blood-brain barrier was disrupted and were the result of stimulation of both H1- and H2-receptors. These responses probably occur within inner layers of arterial smooth muscle; dilatation of pial arterioles to local microapplication of histamine and its receptor agonists indicates that H2-receptors are the predominant type in outer layers of arterial smooth muscle. A segmental profile of histamine receptors within the cerebrovascular bed is suggested as follows: since both H1- and H2-receptors could mediate dilatation of arterioles and arteries, it may be concluded that both types of receptor are present in resistance vessels; in the capillary bed, H2-receptors are the predominant type; capacitance vessels (pial veins) did not respond to perivascular application of histamine or its agonists. These studies suggest that receptors for histamine may be sparsely populated or absent in cerebral venous smooth muscle.