Abstract
Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP), the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.
Highlights
Blood pressure is mainly regulated by vascular peripheral resistance and cardiac output
Vascular tone is mainly modulated by the autonomic nervous system (ANS), with a predominant function of the sympathetic division
The role of nonadrenergic noncholinergic (NANC) neurotransmission on the vascular tone regulation is derived from a number of studies showing that, apart from NA and ACh, several neuromediators released by the ANS participate in the regulation of smooth muscle contractility
Summary
Blood pressure is mainly regulated by vascular peripheral resistance and cardiac output. The role of NANC neurotransmission on the vascular tone regulation is derived from a number of studies showing that, apart from NA and ACh, several neuromediators released by the ANS participate in the regulation of smooth muscle contractility (for a historical perspective, see [4]) This NANC neurotransmission had been mainly related to purinergic [5] and nitrergic [6] transmission. The role of NANC neurotransmission in the resistance vascular function has a predominant vasodilator component, an effect opposite to the contractile effect induced by sympathetic adrenergic stimulation In this case, the most important vasodilator neuromediators are calcitonin generelated peptide (CGRP), substance P (SP), nitric oxide (NO), and adenosine triphosphate (ATP) (see [11]). The neural control of cardiovascular function is mainly associated with activation of autonomic postganglionic nerve fibers, and with activation of primary afferent (peptidergic) sensory fibers (Figure 1) [3, 15, 16]
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