Calcitonin Gene-Related Peptide and Cerebral Blood Vessels: Distribution and Vasomotor Effects

Abstract

Summary: The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are de scribed 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 peri karya containing CGRP immunoreactivity are demon strable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal peri karya, 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 radioimmu noassay. The highest concentrations were observed in ce rebral 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 Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide recently identified from struc tural analysis of the products of calcitonin gene ex pression (Amara et al., 1982;Rosenfeld et al. , 1983). CGRP-immunoreactive fibers are abundant in the sensory receiving areas of the spinal cord and to a lesser extent in the sympathetic and parasym pathetic centers. CGRP-containing terminals are also present in sensory nuclei of the lower brain stem, for example, the nucleus tractus solitarius (Gibson et aI. , 1984; Kawai et aI., 1985;Skofitsch and Jacobowitz, 1985). Immunocytochemical studies have revealed that CGRP coexists with sub stance P and neurokinin A in nerve cell bodies of 720cerebral arteries in all species examined (human pial, fe line middle cerebral, rabbit, guinea pig and rat basilar ar teries). The concentration of CGRP eliciting half-max imal responses ranged from 0.4 nM (human pial artery) to 3 nM (rat and rabbit basilar arteries). Pretreatment of ce rebral arteries with low concentrations of either sub stance P (0.1 nM) or neurokinin A (3 nM) attenuated slightly the CGRP-induced relaxations of guinea pig bas ilar arteries. Calcitonin was found to be a very weak di lator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP ap pear 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.

Regional haemodynamic effects of human α‐ and β‐calcitonin gene‐related peptide in conscious Wistar rats

“…These results are consistent with rat a-CGRP having potent cerebral vasodilator properties (McCulloch et al, 1986;Uddman et al, 1986;Edvinsson et al, 1987) and positive chronotropic effects (Marshall et al, 1986b;Sigrist et al, 1986). One possible explanation of the lack of mesenteric vasodilatation with infusion of CGRP is that reflex effects override the dilator actions of CGRP.…”

Calcitonin Gene-Related Peptide in Serum After Spontaneous Subarachnoid Hemorrhage

“…Finally Edvinsson et al (1987) could confirm that, in cats, the presence of lesions in the trigeminal ganglion prolonged arterial vasoconstriction after SAH (McCulloch et al, 1986). However, six years later, Keller et al (1993) studied the profile of neuropeptides in the dura mater in a singlehemorrhage rodent model.…”

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

“…CGRP is another vasodilator that potentially contributes to cerebral vasodilation produced by cSCS in the same way that it contributes to SCS-induced vasodilation in the limbs . Immunochemical studies show that CGRP containing nerves innervate the cerebrovascular tree (Edvinsson et al, 1987(Edvinsson et al, , 1995Suzuki et al, 1989). Furthermore, stimulation of trigeminal ganglion induced vasodilation mediated by these CGRP containing nerves (Escott et al, 1995).…”