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 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. ABSTRACT: 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 < 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 < 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.

Sites of transition between functional systemic and cerebral arteries of rabbits occur at embryological junctional sites.

The vascular smooth muscle of cerebral blood vessels is relatively insensitive to sympathomimetic stimulation compared with muscle from systemic vessels. The transition in the vertebral artery occurs just rostral to the emergence of that artery from the foramen of the lateral process of the atlas and in the internal carotid artery just before it enters the carotid canal. These sites in the adult correspond to embryological junctions between segments of the vertebral and internal carotid arteries derived from the primitive dorsal aortas and their branches with vessels originating locally from the bilateral longitudinal neural arteries. Topographic patterns of vascular properties may in some cases be explained by the different sites of origin of their primordial mesodermal cells.

Cerebral vasomotor reactivity in Parkinson's disease, multiple system atrophy and pure autonomic failure.

Parkinson's disease (PD), multiple system atrophy (MSA) and pure autonomic failure (PAF) are neurodegenerative disorders frequently associated with orthostatic hypotension and syncope, though with different underlying mechanisms. Cerebral hemodynamic responses in these three neurodegenerative diseases are still incompletely studied and it is possible that they would be differentially affected. We measured blood flow velocity (BFV) in the middle cerebral artery (MCA) and vertebral artery (VA) in patients with these disorders and investigated whether cerebral vasomotor reactivity (VMR) differs in these three disorders. Twenty-four patients (9 with PD, 10 with MSA and 5 with PAF) were studied. VMR was assessed in the MCA and VA, using transcranial Doppler (TCD) and Diamox test (injection of 1 g acetazolamide i.v.) with the patients in a recumbent position. The percent difference between BFV before and after acetazolamide injection was defined as VMR% and the results were compared by ANOVA. The mean MCA and VA blood flow velocities were similar in the three disorders and within normal limits for our laboratory. The mean MCA VMR values were 37.5+/-24.0%, 27.9+/-28.0% and 38.0+/-33.9% in PD, MSA and PAF, respectively. The VA VMR values were 22.9+/-23.6%, 32.4+/-38.0% and 18.9+/-18.3%, respectively, with no significant differences between the groups. We conclude that BFV is normal in PD, MSA and PAF and that the VMR, as investigated by TCD and the Diamox test, did not disclose differences in cerebral vasomotor responses between these conditions.

Separate development of nitric oxide synthase- and vasoactive intestinal polypeptide-immunoreactive nerves arising from the vertebral artery in the rat.

Development of nitric oxide synthase (NOS)-and vasoactive intestinal polypeptide (VIP)-immunoreactive (-IR) nerves supplying the basilar and vertebral arteries (BA and VA) was investigated in White Wistar rats, using double immunohistochemistry. NOS-IR and VIP-IR nerves via the anterior circulation (AC), which mostly expressed NO(+)/VIP(+), extended to the BA during the second postnatal week, and usually reached as far as the rostral two third of the BA on PND 20. NOS-IR nerves were completely lack in the cBA and the VA on PND10, and often absent from these arterial regions even at PND 20. Nevertheless, a small number of VIP(+)/NOS(-) nerves were localized in the walls from the caudal BA (cBA) to the VA on PND 5. On PND 20, they frequently met with the descending NOS-IR and VIP-IR nerves via the AC around the lower portion of the middle BA. Fiber bundles containing NOS(+)/VIP(+) axons were first visualized on the caudal VA at PND 30 and observed frequently at PND 80, with a distinct increase in number of NOS-IR and VIP-IR nerves supplying the cBA and the VA. Thus, NOS-IR nerves coming from the VA develop through its own characteristic sequence that lags markedly behind the time of appearance for VIP-IR nerves from the same vascular route and for NOS-IR and VIP-IR nerves via the AC.

[Effects of endoscopic sympathicotomy in carotid and vertebral arteries in the surgical treatment of primary hyperhidrosis]. / Efeitos da simpaticotomia endoscópica sobre as artérias carótidas e vertebrais na terapêutica cirúrgica da hiperidrose primária.

PURPOSES: Analyze, in patients with primary hyperhidrosis (PH) who was undergone to videothoracoscopic sympathicotomy, the degree of vascular denervation after surgical transection of the thoracic sympathetic chain by measuring ultrasonografic parameters in carotid and vertebral arteries. METHODS: Twenty-four patients with PH underwent forty-eight endoscopic thoracic sympathicotomy and were evaluated by duplex eco-Doppler measuring systolic peak velocity (SPV), diastolic peak velocity (DPV), pulsatility index (PI) and resistivity index (RI) in bilateral common, internal and external carotids, besides bilateral vertebral arteries. The exams were performed before operations and a month later. Wilcoxon test was used to analyse the differences between the variables before and after the sympatholisis. RESULTS: T3 sympathicotomy segment was the most frequent transection done (95.83%), as only ablation (25%) or in association with T4 (62.50%) or with T2 (8.33%). It was observed increase in RI and PI of the common carotid artery (p < 0.05). The DPV of internal carotid artery decreased in both sides (p < 0.05). The SPV and the DPV of the right and left vertebral arteries also increased (p < 0.05). Asymmetric findings were observed so that, arteries of the right side were the most frequently affected. CONCLUSIONS: Hemodynamic changes in vertebral and carotid arteries were observed after sympathicotomy for PH. SPV was the most often altered parameter, mostly in the right side arteries, meaning significant asymmetric changes in carotid and vertebral vessels. Therefore, the research findings deserve further investigations to observe if they have clinical inferences.

Overall distribution of substance P-containing nerves in the wall of the cerebral arteries of the guinea pig and its origins.

The overall distribution of substance P-like immunoreactivity (SPI) in the wall of the cerebral arteries and their origins were investigated in the guinea pig by using whole-mounts. Two types of SPI fibers were seen: one forming dense fiber bands and located among the periadventitial nerves, and the other forming a meshwork. The SPI fibers located in the periadventitial nerves often leave these nerves to form a meshwork of SPI fibers of varying density according to the diameter or location of the blood vessels. The present study suggests that: (1) SPI fibers located on the circle of Willis and its branches originate from SPI cells in the trigeminal ganglion; (2) SPI fibers of the rostral one-third of the basilar artery originate partly from trigeminal SPI cells; and (3) SPI fibers in the caudal two-thirds of the basilar artery originate exclusively from other SPI cells, apart from the trigeminal ganglion.

Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries.

Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1-TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea.

Heterogeneity of neurogenic responses in intra- and extrameningeal arteries of dogs.

1. Neurogenic responses to transmural electrical stimulation were examined in endothelium-denuded extrameningeal (vertebral and carotid) and intrameningeal (spinal, basilar and middle cerebral) arteries isolated from dogs. 2. In the extrameningeal arteries, transmural electrical stimulation produced a phasic contraction. This contraction was abolished by tetrodotoxin, prazosin and guanethidine. However, alpha,beta-methylene ATP and NG-nitro-L-arginine (L-NOARG) had no significant effect on the contractile responses. 3. In the intrameningeal arteries, the neurogenic responses to electrical stimulation were composed of a transient contraction and relaxation. The transient contraction was selectively inhibited by guanethidine L-NOARG abolished the relaxation but not the contraction induced by electrical stimulation. Prazosin had no effect on either neurogenic response. 4. Noradrenaline produced a large contraction in the extrameningeal arteries which was selectively inhibited by prazosin. alpha,beta-Methylene ATP produced neither contraction nor inhibition of the response to noradrenaline in the extrameningeal arteries. 5. In the intrameningeal arteries, alpha,beta-methylene ATP produced a greater contraction than noradrenaline. The response to alpha,beta-methylene ATP was selectively abolished by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP itself. The contractile response to noradrenaline was inhibited by rauwolscine but not by prazosin. 6. ATP produced endothelium-dependent relaxations in the extrameningeal and intrameningeal arteries, which were attenuated by endothelium removal. 7. NADPH diaphorase-positive fibres were dense in the middle cerebral and basilar arteries but rare or absent in the spinal artery. In the extrameningeal arteries diaphorase-positive traces were observed in the vasa vasorum. 8. The present findings indicate that the neurogenic responses of intrameningeal arteries of dogs are composed of NO-ergic and sympathetic purinergic components, while the extrameningeal arteries tested produced only sympathetic adrenergic responses, suggesting that regional heterogeneity may be associated with a sudden transition in innervation and receptor expression at the meninx.

The distribution of adrenergic receptors in cerebral blood vessels: an autoradiographic study.

The first morphological evidence of the existence of adrenergic receptors (alpha 1, alpha 2 and beta) within the vascular walls of the central nervous system were presented using the in vitro receptor autoradiographic technique. In the rat pial arteries all three types of adrenergic receptors were demonstrated, whereas the human pial arteries failed to show significant autoradiographic grains of alpha 1 type of adrenergic receptors indicating a considerable inter-species difference in the distribution of adrenergic receptors. alpha 2 and beta receptors in human pial arteries were found not only in the arterial smooth muscle layers but also in the endothelial layers. This suggests a possibility that circulating sympathomimetic agents play some role in controlling the tone or permeability of vascular walls within the central nervous system. A distinct distribution of alpha 1 receptors in cortical layer IV where the vascular plexus was richest may suggest a relation of alpha 1 receptors and blood flow of brain parenchyma.

Dual innervation of substance P-containing neuron system in the wall of the cerebral arteries.

The present study has shown the presence of substance P-like immunoreactive (SPI) fiber plexuses both in the carotid and vertebrobasilar systems in the Mongolian gerbil, suggesting that the origins of SPI fibers in these two systems differ. The present study further demonstrated in the guinea pig, using experimental manipulations, the dual origin of SPI fibers in the cerebral arteries; one from the trigeminal ganglion (TG) that mainly innervates the carotid system, and the other that separates from the TG and mainly innervates the vertebrobasilar system.

Nerves accompanying the vertebral artery and their clinical relevance.

In elucidating the morphologic basis of cervical spondylosis, the nerves accompanying the vertebral artery were studied under an operative microscope and by means of Karnovsky's histochemical method for acetylcholinesterase (AChE). The results show that the nerves arising from the cervical part of the sympathetic trunk and the cervical nerves anastomose with each other around the artery, and are distributed to the vertebral artery and the cervical spine. The nerves accompanying the vertebral artery show different degrees of AChE activity, and may be compressed or stimulated as a result of disease of Luschka's joint and the other degenerated structures, based on their anatomic relationship.

An investigation of a sympathetic innervation of the vertebral artery in primates: is there a neurogenic substrate for vasoconstriction?

Vasoconstriction of the vertebral artery may be neurogenic in origin. Although the existence of a perivascular sympathetic plexus of the vertebral artery is not in doubt, no method used to date has conclusively demonstrated a direct sympathetic innervation of the vascular smooth muscle cells and, hence, vasomotor function. It was the aim of this study, therefore, to visualise and localise noradrenergic fibres in the wall of the vertebral artery. Intracranial vertebral artery specimens (10 vervet monkeys and 10 baboon vessels) were sectioned (40 mm serial sections) and treated with anti-tyrosine hydroxylase, anti-dopamine b-hydroxylase, and anti-chromogranin-A antibodies. Some evidence of catecholaminergic fibres in the tunica adventitia but not penetrating the external elastic lamina or tunica media of the vertebral artery wall was seen. These findings were confirmed by electron microscopy. It was concluded that although a perivascular sympathetic plexus exists, the vertebral artery of primates was not shown to have a direct sympathetic innervation and a neurogenic vasoconstrictor function is unlikely.

An investigation of an autonomic innervation of the vertebral artery using monoamine histofluorescence.

Blood flow to the hindbrain, via the paired vertebral arteries, must be uncompromised for adequate neurological functioning of its vital centres. Therefore, it would seem unlikely that the intracranial vertebral artery would need to vasoconstrict, thus reducing its blood flow. In order to investigate the existence and location of a noradrenaline-mediated constrictor mechanism in the wall of the intracranial vertebral artery, transverse sections of ten baboon and ten monkey vessels were stained with sucrose-potassium phosphate-glyoxylic acid (counterstained with malachite-green). This method allows the visualisation of catecholaminergic nerves when the sections are exposed to ultraviolet light. In this study of primate vascular tissue, however, none of the monkey or baboon vertebral artery sections showed the presence of noradrenergic nerves in the tunica media - tunica adventitia junction or penetrating the tunica media of the arteries. These findings indicate that the intracranial vertebral artery does not have a neurogenic vasomotor function in primates.

Spinal cord protection by papaverine and intrathecal cooling during aortic crossclamping.

AIM: To extend the safe period of aortic crossclamping in the porcine model by intrathecally dilating the spinal arteries, with cooling of the spinal cord, or using selfoteL METHODS: Experimental design and setting: prospective domestic laboratory pig study. INTERVENTIONS: fifteen animals were assigned to a control group (C, N=5), intrathecal papaverine plus spinal cord cooling group (IP+C, N=5), or selfotel group (S, N=5). In the IP+C group, a lumbar laminectomy was performed and an intrathecal catheter placed for intrathecal injection of papaverine and perfusion with cold Ringer's solution (4 degrees C) prior to aortic crossclamping. In the selfotel group, 20 mg/kg of selfotel was administered 30 minutes before aortic crossclamping. In all 15 animals, the aorta was crossclamped for 60 minutes at normothermia. MEASURES: immediately after the operation and 24 hours later, lower limb function was evaluated. RESULTS: All five control animals were paralyzed; all 5 IP+C animals could stand or walk (p=0.004 versus control); and in the selfotel group, one had paraparesis, three had paraplegia and one died before evaluation (p=n.s.) CONCLUSIONS: The combination of intrathecal papaverine to dilate spinal arteries and prevent spasm from the cold solution plus intrathecally cooling the spinal cord appears to extend the period of safe aortic crossclamping. Selfotel, in this model of extended, severe, spinal cord ischemia, was ineffective.

[A case of effective decompression at the first segment of the vertebral artery for intractable vertigo].

Atherosclerotic change is the main reason for vertebrobasilar insufficiency. However, if clinical symptoms such as vertigo happen transiently and repeatedly with head movement, vascular insufficiency due to mechanical compression of the vertebral artery must be kept in mind as its cause. The patient was a 54-year-old male complaining of recurrent vertigo which occurred during head rotation. He had been treated medically before he came to our hospital. Right compressed vertebral angiogram with head turned to the right and left compressed vertebral angiogram with head turned to the left were obtained at the first segment. Unilateral decompression of the vertebral artery was performed. At surgery it was found that the right vertebral artery was compressed by a stellate ganglion. After cutting of the sympathetic chains, the stellate ganglion was detached from the vertebral artery. The patient's intractable vertigo immediately disappeared after this procedure. It is concluded that if severe vertigo or dizziness is repeated under certain conditions, we must perform a bilateral vertebral angiogram and differentiate whether it is a case of decompression or not and then take measures to bring about decompression effectively.

[Two cases of severe vertigo occasioned by neck rotation and its correlation with the direction of vertebral artery at its origin].

We report two cases of severe vertigo with neck rotation. The first case is that of a 54-year-old woman. She suffered from severe vertigo during neck rotation to the right. Angiography demonstrated that the origin of the left vertebral artery (VA) became kinked when she turned her head to the right. The second case is that of a 59-year-old man. He suffered from severe vertigo during neck rotation to the left. Angiography demonstrated that the kink in the right VA at its origin became worse with the patient's turning his head to the left. We resected nerve fibers from the stellate ganglion at the origin of the respective vertebral arteries and corrected the kink in the arteries at their origin. Both patients were relieved of vertigo after the operation the fact that there was vertigo occasioned by neck rotation. The direction of neck rotation was identical with that of a kink in the VA at its origin in both patients. Therefore, the direction of neck rotation is useful information for the diagnosis of vertigo induced by neck rotation. In terms of the treatment, though vascular reconstruction such as vein graft bypass between the VA and the carotid artery or transposition of the VA onto the subclavian artery has been established for VA stenosis and occlusion, the resection of nerve fiber from the stellate ganglion at the origin of VA is also effective and safe, especially when a kink in the VA at its origin accompanies with neck rotation.

[Effects of stimulation of the vertebral nerve around the proximal vertebral artery on pupil and the autonomic nervous system--a contribution to pathophysiology of Powers' intermittent vertebral artery compression syndrome].

In order to elucidate the pathophysiology involved in Powers' intermittent vertebral artery compression syndrome, the author investigated sympathetic and parasympathetic changes produced by stimulation of nerves around the proximal vertebral artery (the vertebral nerve) in anesthetized and immobilized cats. These changes were observed mainly through pupillary changes, pulse and blood pressure, evoked potentials in the lateral horn of the upper thoracic cord (centrum ciliospinale), in the cervical sympathetic trunk, and in the short ciliary nerve. Electrical stimulation of vertebral nerve and local application of K ion around the vertebral artery produced stimulus-dependent ipsilateral mydriasis; when stimulation of higher strength was applied pronounced ipsilateral and mild contralateral mydriasis and hypertension occurred. Electrical stimulation of perivascular tissue around the subclavian artery proximal to origin of the vertebral artery showed ipsilateral mydriasis; while on stimulating the distal subclavian, the costcervical, the omocervical and the internal thoracic arteries did not show any pupillary response. Neuronal discharges in the lateral horn of upper thoracic cord and in the cervical sympathetic trunk showed stimulus-dependent increases on stimulating the vertebral nerve; while, inhibitory responses were observed in the short ciliary nerve formed by parasympathetic nerve fibers. From the data available, it seems likely that the stimulation of periarterial neural structure of the vertebral artery produced sympathetic excitatory as well as parasympathetic inhibitory neuronal discharges simultaneously may probably be derived from the integrating autonomic center in the hypothalamus.

[The origins of the formation of the initial portion of the vertebral nerve in the cat]. / Istochniki formirovaniia nachal'nogo otdela pozvonochnogo nerva u koshki.

Retrograde transport of horse radish peroxidase revealed the sources of forming of the initial part of the vertebral nerve in cat. The enzyme was applied on the central region of the nerve near its outlet in ganglion stellatum. Most nerve fibers the vertebral nerve contains are the processes of neurons in ganglion stellatum. Bodies of the labeled neurons in the ganglion are located in the area, attached to the site of the vertebral nerve outlet. It also contains certain number of the afferent fibers of the II-VII thoracic segments spinal ganglia. Axons of motor neurons, the bodies of which are located in ventral cornua of the spinal cord II thoracic segments may also be present. Thus, the cat vertebral nerve is mixed in the site of its forming.

[Analysis of the effectiveness of reflexotherapy in patients with osteochondrosis of the cervical spine]. / Analiz éffektivnosti refleksoterapii u bol'nykh osteokhondrozom sheinogo otdela pozvonochnika.

An original method of reflex therapy is depicted. It lies in electric stimulation of the vertebral artery point (along with traditional acupuncture points) with currents alternating in frequency. The positive dynamics attained was supported by the data of instrumental methods, attesting to the improvement of cerebral circulation.

[Influence of the vertebral nerve on several indices of cerebral blood flow]. / Vliianie pozvonochnogo nerva na nekotorye pokazateli mozgovogo krovotoka.

The dogs and rabbits, electrical stimulation of the vertebral nerve reduced the pressure in the carotid and the vertebral--basillar arterial systems leaving the general arterial pressure unaltered. Simultaneously the values of pH, PO2 PCO2, and buffer bases decreased in the blood flowing from the dog brain. The data obtained suggest that stimulation of the vertebral nerve reduces the blood flow in the vertebral artery which, in conditions of occlusion of the contralateral vertebral artery, leads to the circulatory regional hypoxia of the brain.