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Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats

Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examin...

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Published in:The Journal of physiology 2018-08, Vol.596 (16), p.3505-3529
Main Authors: Roloff, Eva v. L., Walas, Dawid, Moraes, Davi J. A., Kasparov, Sergey, Paton, Julian F. R.
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cited_by cdi_FETCH-LOGICAL-c5057-5d8ee5754edd643adbefecd02837510f4d2c269f872488a424856949a8b03d9d3
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container_title The Journal of physiology
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creator Roloff, Eva v. L.
Walas, Dawid
Moraes, Davi J. A.
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Paton, Julian F. R.
description Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre‐hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age‐matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. Our results support a compromised vasodilatory capacity in PHSH and SH rats compared to Wistar rats, which may explain their hypoperfused brainstem. Neurogenic hypertension may result from brainstem hypoperfusion. We previously found remodelling (decreased lumen, increased wall thickness) in vertebrobasilar arteries of juvenile, pre‐hypertensive spontaneously hypertensive (PHSH) and adult spontaneously hypertensive (SH) rats compared to age‐matched normotensive rats. We tested the hypothesis that there would be a greater density of sympathetic to parasympathetic innervation of vertebrobasilar arteries in SH versus Wistar rats irrespective of the stage of development and that sympathetic denervation (ablation of the superior cervical ganglia bilaterally) would reverse the remodelling and lower blood pressure. Contrary to our hypothesis, immunohistochemistry revealed a decrease in the innervation density of noradrenergic sympathetic fibres in adult SH rats (P 
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L. ; Walas, Dawid ; Moraes, Davi J. A. ; Kasparov, Sergey ; Paton, Julian F. R.</creator><creatorcontrib>Roloff, Eva v. L. ; Walas, Dawid ; Moraes, Davi J. A. ; Kasparov, Sergey ; Paton, Julian F. R.</creatorcontrib><description>Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre‐hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age‐matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. Our results support a compromised vasodilatory capacity in PHSH and SH rats compared to Wistar rats, which may explain their hypoperfused brainstem. Neurogenic hypertension may result from brainstem hypoperfusion. We previously found remodelling (decreased lumen, increased wall thickness) in vertebrobasilar arteries of juvenile, pre‐hypertensive spontaneously hypertensive (PHSH) and adult spontaneously hypertensive (SH) rats compared to age‐matched normotensive rats. We tested the hypothesis that there would be a greater density of sympathetic to parasympathetic innervation of vertebrobasilar arteries in SH versus Wistar rats irrespective of the stage of development and that sympathetic denervation (ablation of the superior cervical ganglia bilaterally) would reverse the remodelling and lower blood pressure. Contrary to our hypothesis, immunohistochemistry revealed a decrease in the innervation density of noradrenergic sympathetic fibres in adult SH rats (P &lt; 0.01) compared to Wistar rats. Unexpectedly, there was a 65% deficit in parasympathetic fibres, as assessed by both vesicular acetylcholine transporter (α‐VAChT) and vasoactive intestinal peptide (α‐VIP) immunofluorescence (P &lt; 0.002) in PHSH rats compared to age‐matched Wistar rats. Although the neural activity of the internal cervical sympathetic branch, which innervates the vertebrobasilar arteries, was higher in PHSH relative to Wistar rats, its denervation had no effect on the vertebrobasilar artery morphology or persistent effect on arterial pressure in SH rats. Our neuroanatomic and functional data do not support a role for sympathetic nerves in remodelling of the vertebrobasilar artery wall in PHSH or SH rats. The remodelling of vertebrobasilar arteries and the elevated activity in the internal cervical sympathetic nerve coupled with their reduced parasympathetic innervation suggests a compromised vasodilatory capacity in PHSH and SH rats that could explain their brainstem hypoperfusion. Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre‐hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age‐matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. Our results support a compromised vasodilatory capacity in PHSH and SH rats compared to Wistar rats, which may explain their hypoperfused brainstem.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/JP275973</identifier><identifier>PMID: 29797726</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Acetylcholine ; Animals ; Arteries ; Autonomic nervous system ; Autonomic Nervous System - physiopathology ; Basilar Artery - innervation ; Basilar Artery - metabolism ; Blood pressure ; Brain stem ; Cardiovascular ; cerebrovascular resistance ; Denervation ; Developmental stages ; Fibers ; Functional anatomy ; Ganglia ; Hypertension ; Hypertension - physiopathology ; Immunofluorescence ; Immunohistochemistry ; Innervation ; Intestine ; Male ; Norepinephrine ; parasympathetic innervation ; Parasympathetic nervous system ; rat ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Research Paper ; Rodents ; sympathetic innervation ; Sympathetic nerves ; Vasoactive agents ; Vasoactive intestinal peptide ; Vasodilation ; Veins &amp; arteries ; Vertebral Artery - innervation ; Vertebral Artery - metabolism ; vertebral/basilar arteries ; Vesicular acetylcholine transporter</subject><ispartof>The Journal of physiology, 2018-08, Vol.596 (16), p.3505-3529</ispartof><rights>2018 The Authors. The Journal of Physiology © 2018 The Physiological Society</rights><rights>2018 The Authors. 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L.</creatorcontrib><creatorcontrib>Walas, Dawid</creatorcontrib><creatorcontrib>Moraes, Davi J. A.</creatorcontrib><creatorcontrib>Kasparov, Sergey</creatorcontrib><creatorcontrib>Paton, Julian F. R.</creatorcontrib><title>Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre‐hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age‐matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. Our results support a compromised vasodilatory capacity in PHSH and SH rats compared to Wistar rats, which may explain their hypoperfused brainstem. Neurogenic hypertension may result from brainstem hypoperfusion. We previously found remodelling (decreased lumen, increased wall thickness) in vertebrobasilar arteries of juvenile, pre‐hypertensive spontaneously hypertensive (PHSH) and adult spontaneously hypertensive (SH) rats compared to age‐matched normotensive rats. We tested the hypothesis that there would be a greater density of sympathetic to parasympathetic innervation of vertebrobasilar arteries in SH versus Wistar rats irrespective of the stage of development and that sympathetic denervation (ablation of the superior cervical ganglia bilaterally) would reverse the remodelling and lower blood pressure. Contrary to our hypothesis, immunohistochemistry revealed a decrease in the innervation density of noradrenergic sympathetic fibres in adult SH rats (P &lt; 0.01) compared to Wistar rats. Unexpectedly, there was a 65% deficit in parasympathetic fibres, as assessed by both vesicular acetylcholine transporter (α‐VAChT) and vasoactive intestinal peptide (α‐VIP) immunofluorescence (P &lt; 0.002) in PHSH rats compared to age‐matched Wistar rats. Although the neural activity of the internal cervical sympathetic branch, which innervates the vertebrobasilar arteries, was higher in PHSH relative to Wistar rats, its denervation had no effect on the vertebrobasilar artery morphology or persistent effect on arterial pressure in SH rats. Our neuroanatomic and functional data do not support a role for sympathetic nerves in remodelling of the vertebrobasilar artery wall in PHSH or SH rats. The remodelling of vertebrobasilar arteries and the elevated activity in the internal cervical sympathetic nerve coupled with their reduced parasympathetic innervation suggests a compromised vasodilatory capacity in PHSH and SH rats that could explain their brainstem hypoperfusion. Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre‐hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age‐matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. 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Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. Our results support a compromised vasodilatory capacity in PHSH and SH rats compared to Wistar rats, which may explain their hypoperfused brainstem. Neurogenic hypertension may result from brainstem hypoperfusion. We previously found remodelling (decreased lumen, increased wall thickness) in vertebrobasilar arteries of juvenile, pre‐hypertensive spontaneously hypertensive (PHSH) and adult spontaneously hypertensive (SH) rats compared to age‐matched normotensive rats. We tested the hypothesis that there would be a greater density of sympathetic to parasympathetic innervation of vertebrobasilar arteries in SH versus Wistar rats irrespective of the stage of development and that sympathetic denervation (ablation of the superior cervical ganglia bilaterally) would reverse the remodelling and lower blood pressure. Contrary to our hypothesis, immunohistochemistry revealed a decrease in the innervation density of noradrenergic sympathetic fibres in adult SH rats (P &lt; 0.01) compared to Wistar rats. Unexpectedly, there was a 65% deficit in parasympathetic fibres, as assessed by both vesicular acetylcholine transporter (α‐VAChT) and vasoactive intestinal peptide (α‐VIP) immunofluorescence (P &lt; 0.002) in PHSH rats compared to age‐matched Wistar rats. Although the neural activity of the internal cervical sympathetic branch, which innervates the vertebrobasilar arteries, was higher in PHSH relative to Wistar rats, its denervation had no effect on the vertebrobasilar artery morphology or persistent effect on arterial pressure in SH rats. Our neuroanatomic and functional data do not support a role for sympathetic nerves in remodelling of the vertebrobasilar artery wall in PHSH or SH rats. The remodelling of vertebrobasilar arteries and the elevated activity in the internal cervical sympathetic nerve coupled with their reduced parasympathetic innervation suggests a compromised vasodilatory capacity in PHSH and SH rats that could explain their brainstem hypoperfusion. Key points Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre‐hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age‐matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. 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ispartof The Journal of physiology, 2018-08, Vol.596 (16), p.3505-3529
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language eng
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source PubMed Central Free; Wiley-Blackwell Read & Publish Collection
subjects Acetylcholine
Animals
Arteries
Autonomic nervous system
Autonomic Nervous System - physiopathology
Basilar Artery - innervation
Basilar Artery - metabolism
Blood pressure
Brain stem
Cardiovascular
cerebrovascular resistance
Denervation
Developmental stages
Fibers
Functional anatomy
Ganglia
Hypertension
Hypertension - physiopathology
Immunofluorescence
Immunohistochemistry
Innervation
Intestine
Male
Norepinephrine
parasympathetic innervation
Parasympathetic nervous system
rat
Rats
Rats, Inbred SHR
Rats, Wistar
Research Paper
Rodents
sympathetic innervation
Sympathetic nerves
Vasoactive agents
Vasoactive intestinal peptide
Vasodilation
Veins & arteries
Vertebral Artery - innervation
Vertebral Artery - metabolism
vertebral/basilar arteries
Vesicular acetylcholine transporter
title Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats
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