Increases in NPY in non-sympathetic nerve fibres supplying rat mesenteric vessels after immunosympathectomy

doi:10.1016/0167-0115(91)90223-4

Regulatory Peptides

Volume 34, Issue 1, 11 June 1991, Pages 43-54

https://doi.org/10.1016/0167-0115(91)90223-4 Get rights and content

Abstract

The effect of nerve growth factor (NGF) deprivation on developing peripheral peptide-containing nerves has been examined in Wistar rats. Animals were treated from birth for 7 days with antibodies to NGF (10 μl/g body weight) and killed at 4 or 8 weeks of age. The nerves of the mesenteric and femoral blood vessels, vas deferens and bladder were viewed with histochemical and immunohistochemical techniques. The effectiveness of anti-NGF treatment was monitored by viewing catecholamine (CA)-containing nerves, which were virtually absent from the blood vessels, but were little affected in the vas deferens and bladder in both age groups. Immunoreactivity for substance P and calcitonin gene-related peptide was slightly reduced in the blood vessels. Immunoreactivity for neuropeptide Y (NPY) was reduced in the femoral blood vessels by 88% at both ages, but reductions in NPY immunoreactivity (NPY-IR) in the mesenteric vessels varied with age. In the mesenteric artery at 4 weeks, NPY-IR was reduced by 96% from control values, but at 8 weeks it was reduced by only 37%. Acute sympathectomy with 6-OHDA treatment reduced NPY-IR in the mesenteric artery by 98% at 4 weeks and 93% at 8 weeks. It is proposed that the increase in NPY-IR but not CA-containing nerves in the mesenteric artery between 4 and 8 weeks after immunosympathectomy is due to compensatory innervation from a non-sympathetic source (probably enteric neurons) that is available to mesenteric, but not to femoral blood vessels.

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Citation Excerpt :
Mesenteric arterioles are richly innervated [1,12,17,32,34,35,57,59,60], a finding confirmed by our observations of numerous PGP9.5-ir axons. This mesenteric plexus is comprised of multiple axon types including noradrenergic, nitrergic, peptidergic, and cholinergic fibers [1,5,17,18,32,34,35,57,60]. A significant sensory innervation originates from the thoracic dorsal root ganglia [12,34,35,59,60,67], consistent with our observation of CGRP-ir innervation.
Differences exist in vascular function and disease susceptibility in males and females, and estrogen is apparently a primary factor. One mechanism by which estrogen may influence vascular function is by affecting vasomotor innervation. We have shown previously that estrogen increases calcitonin gene-related peptide (CGRP)-immunoreactive sensory innervation of the rat mammary gland, but it is not known if this occurs in other tissues. The objective of this study was to determine if estrogen modulates CGRP-immunoreactive innervation of vascular and non-vascular tissues. Ovariectomized adult virgin female rats were implanted with pellets containing 17β-estradiol or placebo. After 7 days, innervation was examined in the external ear, jejunal mesenteric arterioles, superficial epigastric, femoral, and uterine arteries, and foot skin. Immunofluorescence microscopy of the external ear pinna revealed increased CGRP-immunoreactive sensory innervation in estrogen-treated rats, and this was attributable specifically to increased innervation of arterioles. Tyrosine hydroxylase-immunoreactive innervation was unchanged. Total nerve density, revealed by the pan-neuronal marker PGP 9.5, was also greater after estrogen treatment, implying structural proliferation of nociceptor vasodilator fibers. Mesenteric arteriolar CGRP-immunoreactive nerve density was also selectively increased by estrogen treatment. However, estrogen did not affect CGRP-immunoreactive nerve density of superficial epigastric, femoral, or uterine arteries, or foot skin. Therefore, estrogen increases sensory innervation of arterioles, but not of large arteries or skin. We conclude that sensory nociceptor vasodilatory innervation of arterioles is selectively enriched by estrogen, which may influence cardiovascular function in health and disease.
Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin
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Research using animal models of neuropathic pain has revealed sympathetic sprouting onto dorsal root ganglion cells. More recently, sensory fibre sprouting onto dorsal root ganglion cells has also been observed. Previous work in our laboratory demonstrated persistent sympathetic fibre sprouting in the skin of the rat lower lip following sensory denervation of this region. Therefore, we applied immunocytochemistry to determine the effects of sympathectomies on the terminal fields of sensory fibres. The superior cervical ganglia were removed bilaterally and the effects on the innervation of the skin of the rat lower lip were observed 1, 2, 3, 4, 6 and 8 weeks post-surgery. Substance P and dopamine-β-hydroxylase immunoreactivities were used to identify a subset of sensory and sympathetic fibres, respectively. We also assessed neurokinin-1 receptor immunoreactivity. Quantitative data was obtained with the aid of an image analysis system.
In controls, the epidermis and upper dermis were innervated by substance P-immunoreactive fibres only and upper dermal blood vessels possessed the highest density of neurokinin-1 receptor immunoreactivity. Blood vessels in the lower dermis were innervated by both substance P- and dopamine-β-hydroxylase-immunoreactive fibres. Following sympathectomies, substance P-immunoreactive fibres in the epidermis and upper dermis were more intensely labelled only 1 and 2 weeks post-surgery when compared to sham controls. The length of substance P-immunoreactive fibres in this region was also increased only on the second week. Neurokinin-1 receptor immunoreactivity in the upper dermis was slightly decreased 1 and 2 weeks post-surgery. In the lower dermis, substance P-immunoreactive fibres associated with blood vessels were more intensely labelled only 1 and 2 weeks post-surgery, and at all post-surgical time points studied, blood vessels in this region were devoid of dopamine-β-hydroxylase-immunoreactive fibres. The length of substance P-immunoreactive fibres was increased from the first to the third week post-surgery in the lower dermis.
These results indicate that sympathectomies lead to transient changes in substance P-immunoreactive fibre innervation and neurokinin-1 receptor expression in rat lower lip skin. The effects are most prominent in the lower dermis probably due to a greater local concentration of nerve growth factor in this region. The plasticity of the interactions between sensory and sympathetic fibres may prove important in the regulation of skin microcirculation and in the generation of painful sensations under normal conditions or following peripheral nerve injuries.
NPY/sympathetic and NPY/VIP innervation of the blood vessels supplying rat tooth-related structures: Effects of sympathectomy
1999, Neuropeptides
In order to better understand the regulation of blood flow to tooth-related structures, the patterns of VIP- and NPY-ergic innervations in the rat were examined. Nerve fibers showing NPY-like immunoreactivity (NPY-LI) frequently occurred in the walls of the large main arteries, as well as in association with the arterioles, to a high degree co-existing with tyrosine hydroxylase (TH), whereas VIP-LI was mainly restricted to the walls of the large arteries. After sympathectomy, no NPY/TH-LI nerve fibers were seen in blood vessel walls. However, a NPY-immunoreactive nerve population remained in the walls of the large arteries, NPY- and VIP-LI co-existing in this nerve population. Both immunoreactions were intense. The present study suggests that a NPY/sympathetic innervation as well as a VIP innervation (large arteries) are likely to have substantial roles in the balance and maintenance of vasoregulation in tooth-related structures and that a NPY/VIP innervation becomes of particular importance when the NPY/sympathetic innervation is destroyed.
c-Fos in enteric nerves after extrinsic denervation of guinea pig ileum
1999, Journal of Surgical Research
Background.Gastrointestinal function is controlled partly by an interaction between extrinsic (sympathetic, parasympathetic, sensory) and intrinsic (enteric) nerves. However, normal gut function occurs in the absence of extrinsic innervation as enteric nerves adapt to the loss of extrinsic nerves from the gut wall. Expression of the proto-oncogene product, c-Fos, is a signal for activity-dependent changes in gene expression and immunocytochemical detection of c-Fos is used as a marker for changes in neuronal activity. The purpose of this study was to determine if enteric neurons in guinea pig ileum respond to loss of extrinsic innervation by expressing c-Fos protein.
Materials and methods.Fos protein was localized using immunohistochemical methods and an antiserum raised against synthetic Fos. Segments of ileum were extrinsically denervated by crushing the mesenteric nerves in anesthetized animals or by treating animals with 6-hydroxydopamine (6-OH-DA) or capsaicin to destroy sympathetic and extrinsic sensory nerves, respectively.
Results.One week after surgical extrinsic denervation of loops of ileum, 12 ± 1 nuclei/submucosal ganglion and 114 ± 6 nuclei/myenteric ganglion contained Fos immunoreactivity (ir). These values were greater (P< 0.05) than those from unoperated segments from the same animals (4 ± 1 Fos-ir nuclei/submucosal ganglion and 13 ± 4 Fos-ir nuclei/myenteric ganglion) or from sham-operated segments. Significantly more nuclei contained Fos-ir at 4, 7, 10, and 24 weeks after denervation. Finally, capsaicin or 6-OH-DA treatment increased the number of Fos-ir nuclei in enteric ganglia.
Conclusions.These data suggest that Fos expression may be part of the adaptation of enteric nerves to extrinsic denervation.
Neuroreceptor mRNA expression in the rat mesenteric artery develops independently of innervation
1999, International Journal of Developmental Neuroscience
Studies in autonomic targets have shown that nerves may be required for the development and maintenance of postsynaptic receptor populations. We have examined this relationship in the rat mesenteric artery, assessing mRNA expression levels for a range of neuroreceptors after neonatal sympathectomy, using 6-hydroxydopamine or antisera directed against nerve growth factor, and sensory denervation, using capsaicin. Total RNA was extracted from 28 day old rats and reverse transcription-polymerase chain reaction was performed, using primers specific for the α_1(A,B,D)- and α_2(A,B,C)-adrenergic, neurokinin (NK1–NK3), muscarinic (M1–M5) and P_2X purinergic (P_2X1–7) receptor families. Results showed no decreases in mRNA expression of any of the specific receptor subtypes after either sympathetic or sensory denervation. Small increases in mRNA expression were detected following sensory denervation for some of the receptor subtypes. We conclude that neither sympathetic nor sensory nerves are mandatory for the expression of mRNA of a range of neuroreceptors in the mesenteric vascular bed of the rat.
Parasympathetic varicosity proliferation and synaptogenesis in rat eyelid smooth muscle after sympathectomy
1998, Brain Research
Parasympathetic innervation to eyelid smooth muscle inhibits sympathetic neurotransmission pre-junctionally without appreciable direct post-junctional effects. However, 5 weeks after sympathectomy, parasympathetic stimulation elicits substantial cholinergically mediated contractions. This study examined ultrastructural changes accompanying the conversion to parasympathetic excitation. In intact muscles, 64±9 nerve varicosities were encountered per 10⁴μm². Most were close to muscle cells and not fully enclosed by supporting cells. Axo–axonal synapses were observed occasionally. Two days following sympathectomy, varicosity numbers were reduced by 97% and, relative to controls, remaining varicosities were farther from muscle cells and more frequently fully enclosed by supporting cells, but contained greater numbers of small spherical and large dense vesicles. By 6 weeks post-sympathectomy, numbers of varicosities per unit muscle volume increased to 14% of controls. These varicosities differed from those at 2 days in being closer to smooth muscle cells, less frequently enclosed, and having fewer small vesicles. These findings indicate that intact eyelid smooth muscle varicosities are predominantly sympathetic, but a small number of parasympathetic varicosities are present, some of which may form pre-junctional synapses with sympathetic nerves. Between 2 days and 6 weeks post-sympathectomy, varicosities increased in number and established appositions with smooth muscle cells. This suggests that parasympathetic nerves are capable of re-innervating an atypical smooth muscle target after sympathectomy, and that parasympathetic synaptogenesis is likely to contribute to conversion from pre-junctional inhibition to post-junctional excitation after sympathectomy.

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Increases in NPY in non-sympathetic nerve fibres supplying rat mesenteric vessels after immunosympathectomy

Abstract

Dev. Brain Res.

Neurosci. Lett.

Neurosci. Lett.

Neuroscience

Neurosci. Lett.

Brain Res.

Regul. Pept.

Neurosci. Lett.

Neurosci. Lett.

Neuroscience

Neurosci. Lett.

Neuroscience

Nerve growth factor

Physiol. Rev.

Excessive growth of the sympathetic ganglia evoked by a protein isolated from mouse salivary glands

Effect of immunosympathectomy on peripheral sympathetic nerves of rat

J. Auton. Nerv. Syst.

Dorsal root ganglion neurons are destroyed by exposure in utero to maternal antibody to nerve growth factor

Science

The effects of nerve growth factor and its antiserum on the postnatal development and survival after injury of sensory neurons in rat dorsal root ganglia

J. Neurosci.

Persistence of anti-NGF induced dorsal root axons: possible penetration into the mammalian spinal cord

Brain Res.