Calcitonin gene-related peptide and substance P contribute to reduced blood pressure in sympathectomized rats

Abstract

DiPette. Calcitonin gene-related peptide and substance P contribute to reduced blood pressure in sympathectomized rats. Am J Physiol Heart Circ Physiol 289: H1169 -H1175, 2005. First published May 6, 2005; doi:10.1152/ajpheart.00973.2004.-CGRP and substance P (SP) are produced in dorsal root ganglia (DRG) sensory neurons and modulate vascular tone. Sympathetic and sensory nerves compete for NGF, a potent stimulator of CGRP and SP, and it has been suggested that sympathetic hyperinnervation in spontaneously hypertensive rats may reduce the availability of NGF to sensory nerves, thus reducing CGRP and SP. The purpose of this study was to determine whether destruction of peripheral sympathetic nerves in normal rats would increase the availability of NGF for sensory neurons and enhance expression of CGRP and SP. Sympathectomy was produced in rats by guanethidine sulfate administration. Control rats received saline. Sympathectomized rats displayed reductions in blood pressure (BP) and atria norepinephrine levels, whereas NGF levels in the DRG, spleen, and ventricles were increased. Sympathectomy also enhanced CGRP and SP mRNA and peptide content in DRG. Administration of CGRP and SP receptor antagonists increased the BP in sympathectomized rats but not in the controls. Thus sympathectomy enhances sensory neuron CGRP and SP expression that contributes to the BP reduction.guanethidine; blood pressure; peripheral nervous system; nerve growth factor CALCITONIN GENE-RELAXED PEPTIDE (CGRP) and substance P (SP) are potent vasodilator neuropeptides that have been implicated in the regulation of regional organ blood flows and blood pressure (BP), both under normal physiological conditions and in hypertension (6,7,9,10,15,16,36,43,54). Immunoreactive CGRP (iCGRP), SP (iSP), and their receptors are widely distributed in the nervous and cardiovascular systems (6,7,9,10,15,16,23,54). A prominent site of CGRP and SP production is the dorsal root ganglia (DRG) that contain the cell bodies of sensory nerves that terminate peripherally in blood vessels and in other tissues innervated by the sensory nervous system and that terminate centrally in the dorsal horn of the spinal cord. A dense perivascular CGRP and SP neural network is seen around the blood vessels in all vascular beds. In these vessels, CGRP and SP containing nerves are found at the junction of the adventia and the media passing into the muscle layer (6,9,10,15,16,23,54). Indeed, these peptides are often colocalized in the same peripheral nerve terminals. CGRP and SP are released tonically and circulate normally in humans and animals (6,9,15,25,26,54). Plasma CGRP is largely derived from perivascular nerve terminals and is thought to represent a spillover phenomenon related to the release of these peptides to promote vasodilation or other functions. Plasma SP also comes from these perivascular nerve terminals as well as the intestine. Receptors for CGRP have been identified in the endothelial layer, media, and intima of resistance vessels, whereas SP receptors [neurokini...

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“…Based on studies in developing rats, the appearance of peptidergic fibers generally occurs within the skeleton around the same time as the initiation of mineralization [87]. Peptidergic sensory fibers release neuropeptides including calcitonin gene-related peptide (CGRP) and substance P which are potent vasodilators [118, 119] and osteoanabolic [120, 121]. There are also reports that CGRP and substance P can stimulate adipocyte lipolysis [122, 123].…”

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