Peptide‐containing nerve fibers in human cerebral arteries: Immunocytochemistry, radioimmunoassay and in vitro pharmacology

Abstract

Nerve fibers containing neuropeptide Y, vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were seen in the adventitia or at the adventitia-media border of human cerebral arteries obtained during neurosurgical procedures. Radioimmunoassay of human cerebral arteries, removed at autopsy, revealed that the levels of the four peptides did not differ among the major cerebral arteries. There was, however, a gradual decline in peptide concentrations with increasing age of the patients, as measured in the proximal part of the middle cerebral artery. Pharmacological experiments on fresh segments of cerebral (pial) arteries in vitro revealed that neuropeptide Y caused vasoconstriction per se but did not potentiate the contractile response of noradrenaline. VIP, peptide histidine methionine-27 (PHM-27), SP, neurokinin A (NKA), and human CGRP potently relaxed vessels precontracted by prostaglandin F2 alpha, the relative potency being human CGRP greater than SP greater than VIP greater than NKA greater than PHM-27. The amount of relaxation varied between 55% (SP) and 96% (human CGRP) of the prostaglandin F2 alpha-induced contraction. The peptide effects were not antagonized by propranolol, atropine, or cimetidine, suggesting an action that does not involve adrenergic, cholinergic, or histaminergic receptors.

Effect of subarachnoid hemorrhage on calcitonin gene-related peptide-induced relaxation in rabbit basilar artery.

“…8 -23 -26 Such studies have shown that CGRP circulates in human plasma, is released mainly from perivascular nerves, 8 -24 and that nerve fibers containing CGRPlike immunoreactivity are found in the walls of human cerebral arteries. 13 Considering these findings, it is consistent that CGRP is a potent vasodilator in human vessels also. Moreover, it is likely that CGRP has an important role in the regulation of the cerebral circulation and that CGRP may have some therapeutic potential in vascular disease, such as vasospasm after SAH.…”

“…In our study, rabbit basilar artery was relaxed by CGRP independent of the endothelium; this may be due to species and regional differences. There have been several studies performed in human vessels in vitro, 10 " 13 and clinical studies were carried out by several investigators. 8 -23 -26 Such studies have shown that CGRP circulates in human plasma, is released mainly from perivascular nerves, 8 -24 and that nerve fibers containing CGRPlike immunoreactivity are found in the walls of human cerebral arteries.…”

Structure and immunohistochemistry of the human lenticulostriate arteries

“…A positive immune reaction was also registered against SY, a protein in the presynaptic vesicles, and against NF protein, which forms the intermediate cytoskeletal filaments in the axons [2]. The axon terminals are often located close to the media coat, where they may form functional junctions with the SMC [5,27].…”

“…norepinephrine (NE) and dopamine (DA), as well as AChE. Other authors revealed the existence of those and some other neurotransmitters in the LSAs wall, including NO and 5-HT [3,9,11], as well as certain neuropeptides in the perforating arteries, particularly neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), gamma-aminobutyric acid (GABA), substance P (SP), vasoactive intestinal polypeptide (VIP), and brain natriuretic peptide (BNP) [3,5,9,10,17,23,26]. The neurotransmitters and neuropeptides, released from the adventitial nerve fibers, bind to the corresponding membrane receptors of the SMC to exert their action, i.e.…”

“…There is a large body of the literature concerning the LSAs microanatomy, including their capsular and ganglionic regions of supply [13,22,29]. However, structure and immunohistochemistry of the LSAs or other perforating vessels of humans, as well as of some animals, were usually examined superficially, only as a necessary background of certain investigations, especially those regarding their vascular innervation or some cerebrovascular diseases and disorders [1,5,6,9,14,18,28]. Thus, to our knowledge, there is not any article in the last few decades which is specifically devoted to the LSAs structure or general immunohistochemistry.…”