Demonstration of Neuropeptide Containing Nerves and Vasomotor Responses to Perivascular Peptides in Human Cerebral Arteries

Cephalalgia ◽  
1994 ◽  
Vol 14 (2) ◽  
pp. 88-96 ◽  
Author(s):  
L Edvinsson ◽  
I Jansen ◽  
M Cunha e Sa ◽  
S Gulbenkian

A rich supply of nerve fibers containing neuropeptide Y-like (NPY-LI) and tyrosine hydroxylase-like immunoreactivity was seen in human cerebral arteries, arterioles and veins. Only a sparse supply of vasoactive intestinal polypeptide (VIP-LI), substance P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was demonstrated in the walls of human cerebral vessels. In isolated ring segments of human cerebral arteries, NPY and noradrenaline caused vasoconstriction but did not potentiate each other. VIP, peptide histidine methionine, SP, neurokinin A, and CGRP relaxed arteries precontracted by prostaglandin F2a. The degree of innervation and the vasomotor responses are discussed in relation to migraine pathophysiology.

1987 ◽  
Vol 7 (6) ◽  
pp. 720-728 ◽  
Author(s):  
L. Edvinsson ◽  
R. Ekman ◽  
I. Jansen ◽  
J. McCulloch ◽  
R. Uddman

The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are described for a number of different mammalian species. CGRP-immunoreactive nerve fibers were present in the adventitia of cerebral arteries in all species examined (guinea pig, cat, rabbit, rat, and mouse). Numerous perikarya containing CGRP immunoreactivity are demonstrable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal perikarya, CGRP is often colocalized with substance P and neurokinin A. Marked interspecies differences exist both in the density of CGRP-immunoreactive nerve fibers and in the cerebrovascular levels measured with radioimmunoassay. The highest concentrations were observed in cerebral vessels from guinea pigs, the lowest concentration in rabbit vessels, and intermediate levels in the feline and human cerebral vasculature. CGRP is a potent dilator of cerebral arteries in all species examined (human pial, feline middle cerebral, rabbit, guinea pig and rat basilar arteries). The concentration of CGRP eliciting half-maximal responses ranged from 0.4 n M (human pial artery) to 3 n M (rat and rabbit basilar arteries). Pretreatment of cerebral arteries with low concentrations of either substance P (0.1 n M) or neurokinin A (3 n M) attenuated slightly the CGRP-induced relaxations of guinea pig basilar arteries. Calcitonin was found to be a very weak dilator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP appear to be present in all mammalian species (although to varying degrees) and CGRP is invariably a potent dilator of the cerebral arteries for all species.


Cephalalgia ◽  
1992 ◽  
Vol 12 (5) ◽  
pp. 280-283 ◽  
Author(s):  
Jan Erik Hardebo

The vasoreactivity of the intracranial segment of the internal carotid artery to transmitters, present in the perivascular sympathetic, parasympathetic and sensory nerves, as well as to other vasoactive agents of relevance for headache, was tested in man and monkey. The total arterial segment from both species is equipped with contractile receptors for noradrenaline, serotonin, prostaglandin F2a, ergotamine and sumatriptan. Further, the total arterial segment dilated upon exposure to calcitonin gene-related peptide in both species. Other vascoactive transmitters, acetylcholine, substance P and neurokinin A, caused only weak dilatation, restricted to the proximal extracavernous segment in the monkey. The findings are discussed in relation to the pathogenesis and treatment of cluster headache.


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