Facial nerve activity disrupts psychomotor rhythms in the forehead microvasculature.

Forehead blood flow was monitored in seven participants with a unilateral facial nerve lesion during relaxation, respiratory biofeedback and a sad documentary. Vascular waves at 0.1Hz strengthened during respiratory biofeedback, in tune with breathing cycles that also averaged 0.1Hz. In addition, a psychomotor rhythm at 0.15Hz was more prominent in vascular waveforms on the denervated than intact side of the forehead, both before and during relaxation and the sad documentary. These findings suggest that parasympathetic activity in the facial nerve interferes with the psychomotor rhythm in the forehead microvasculature.

Bright light activates a trigeminal nociceptive pathway.

Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.

Cold stimulation induces different responses of ophthalmic artery blood flow velocity depending on baseline blood pressure and gender.

Earlier, we have introduced the spectral index (SI), which was derived from the harmonic content of the blood flow velocity envelope of the ophthalmic artery. SI changed in dependency on the baseline blood pressure (bBP). We now examined SI during sympathetic activation by cold stimulation for 300 s in dependency on bBP to investigate the response to sympathetic neural activity in arterial hypertension. Ten men and 12 women with normal bBP (age, 60.5+/-4.6 years and 61.9+/-7.2 years) and age-adjusted men and women with increased bBP underwent the cold pressor test, including a periodical measurement of blood pressure and blood flow velocity in the ophthalmic artery, the latter by pulsed Doppler sonography. From this, the course of the SI was calculated. During cold stimulation men with increased bBP achieved their SI peak and their systolic blood pressure peak earlier than those with normal bBP (P=0.002 and P=0.035, respectively) and their SI slope was steeper than in normotensive men (P=0.002). Multiple testing showed that the difference of SI decrease between men with normal and increased bBP occurs on average 60 s after the beginning of cold stimulation (P=0.018). These differences were not found between female blood pressure groups, but the results in women may be influenced by antihypertensive treatment of some of the hypertensive women. In conclusion, the SI is useful to evaluate the response to sympathetic activation in hypertensive men but a larger study population should confirm the study results in women.

Human orbital sympathetic nerve pathways.

PURPOSE: To determine pathways of sympathetic nerves from the orbital apex to the eyelids in human cadaver tissue using immunohistochemistry. METHODS: Human cadaver orbit tissue was sectioned and immunolabeled with a monoclonal antityrosine hydroxylase antibody. RESULTS: In the orbital apex, the nasociliary, frontal, lacrimal, and maxillary branches of the trigeminal nerve demonstrated intense staining upon entering the orbit. Immunoreactive axons from the nasociliary and frontal nerves were observed to join the extraocular motor nerves in the posterior orbit. A plexus of immunolabeled nerves was observed to accompany the ophthalmic artery as it entered the orbital apex. The ophthalmic artery and its branches throughout the orbit demonstrated staining of nerve fibers in the peripheral muscularis. The nasociliary nerve contributed sympathetic branches to the ciliary ganglion. Nerves passing through the ciliary ganglion and a few ganglion cell bodies demonstrated mild to moderate tyrosine hydroxylase reactivity. Axons within the short and long ciliary nerves demonstrated strong tyrosine hydroxylase reactivity and were observed to enter the posterior sclera and the suprachoroidal space. The lacrimal gland demonstrated mild pericapillary staining and occasional stromal nerve fibers reactive to the antityrosine hydroxylase antibody. Müller muscle and the inferior tarsal muscle possessed a strong tyrosine hydroxylase-reactive nerve supply that appeared to originate from the anterior terminal branches of the nasociliary and lacrimal nerves. CONCLUSIONS: Sympathetic nerves enter the orbit via the first and second divisions of the trigeminal nerve and a plexus of nerves surrounding the ophthalmic artery. Extraocular motor nerves receive a sympathetic nerve supply from the sensory nerves in the posterior orbit. Some ciliary ganglion cell bodies demonstrated tyrosine hydroxylase-like reactivity, suggesting a sympathetic modulatory role for the ciliary ganglion. Sympathetics innervate ocular structures via the posterior ciliary nerves. Sympathetic axons travel anteriorly in the orbit via the nasociliary and lacrimal nerves to innervate the sympathetic eyelid muscles. Sympathetic nerves also travel with the frontal branch of the ophthalmic nerve to innervate the forehead skin. The ophthalmic artery and all of its branches contain a perivascular sympathetic nerve supply that may be involved in regulation of blood flow to ocular and orbital structures.

Access of autonomic nerves through the optic canal, and their orbital distribution in man.

The notion that autonomic nerves from the internal carotid plexus are transmitted to the orbit with the ophthalmic artery through the optic canal has been variously assumed, disregarded, or denied, but never demonstrated. The objective of this study was to examine the contents of the canal, identify any autonomic nerves, and follow their passage within the orbit. The soft tissues of the optic canal, and the apical tissues of the orbit were removed and examined histologically using 10 cadaver preparations. Additionally, tissues from an orbital exenteration and 10 ocular enucleation or donor specimens were prepared. Some of the latter material was examined with an electron microscope. Numerous autonomic nerves (four to 25, ranging in diameter from 23 to 130 microm) entered the orbit from the internal carotid plexus in the periosteum of the optic canal, the optic nerve dura mater, or the adventitia of the ophthalmic artery. In the orbit they advanced in the loose connective tissue covering the optic nerve dura and joined ciliary nerves close to the eye or entered the eye directly. None were observed to penetrate the dura, apart from a nerve accompanying the central retinal artery. Others were distributed with the ophthalmic artery and its branches. It is concluded that the optic canal is a regular, and often major, route for autonomic nerve distribution to the eye and orbit.

Evidence for nitroxidergic innervation in monkey ophthalmic arteries in vivo and in vitro.

In anesthetized monkeys, electrical stimulation (ES) of the pterygopalatine or geniculate ganglion dilated the ipsilateral ophthalmic artery (OA). The induced vasodilatation was unaffected by phentolamine but potentiated by atropine. Intravenous N(G)-nitro-L-arginine (L-NNA) abolished the response, which was restored by L-arginine. Hexamethonium-abolished vasodilator responses induced solely by geniculate ganglionic stimulation. The L-NNA constricted OA; L-arginine reversed the effect. Destruction of the pterygopalatine ganglion constricted the ipsilateral artery. Helical strips of OA isolated under deep anesthesia from monkeys, denuded of endothelium, responded to transmural ES with relaxations, which were abolished by tetrodotoxin and L-NNA but were potentiated by atropine. It is concluded that neurogenic vasodilatation of monkey OA is mediated by nerve-derived nitric oxide (NO), and the nerve is originated from the ipsilateral pterygopalatine ganglion that is innervated by cholinergic neurons from the brain stem via the geniculate ganglion. The OA appears to be dilated by mediation of NO continuously liberated from nerves that receive tonic discharges from the vasomotor center. Acetylcholine liberated from postganglionic cholinergic nerves would impair the release of neurogenic NO.

Neurogenic vasoconstriction as affected by cholinergic and nitroxidergic nerves in dog ciliary and ophthalmic arteries.

PURPOSE: To determine the involvement of noradrenergic and other vasoconstrictor nerves in the contraction of ocular arteries and the modification by cholinergic and nitroxidergic nerves of vasoconstrictor nerve function. METHODS: Changes in isometric tension were recorded in helical strips of the canine posterior ciliary and external ophthalmic arteries denuded of the endothelium, which were stimulated by transmurally applied electrical pulses (5 Hz). Vasoconstrictor mediators were analyzed by pharmacological antagonists, such as prazosin, alpha,beta-methylene ATP, a P2alpha-purinoceptor antagonist, and BIBP3226, a neuropeptide Y receptor antagonist. RESULTS: Transmural electrical stimulation produced contractions that were potentiated by N(G)-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The contraction was partially inhibited by prazosin and abolished by combined treatment with alpha,beta-methylene ATP but was not influenced by BIBP3226. Stimulation-induced contraction was attenuated by physostigmine and potentiated by atropine. Contractions induced by exogenous ATP were reversed to relaxations by alpha,beta-methylene ATP. In the strips treated with L-NA, prazosin, and alpha,beta-methylene ATP, the addition of L-arginine elicited relaxations by nerve stimulation. The ATP-induced relaxation was attenuated by aminophylline, whereas neurogenic relaxation was unaffected. CONCLUSIONS: Ciliary and ophthalmic arterial contractions by nerve stimulation are mediated by norepinephrine and ATP, which stimulate alpha1-adrenoceptor and P2X purinoceptor, respectively. ATP from the nerve is unlikely involved in vasodilatation. Acetylcholine derived from the nerve impairs the neurogenic contraction, possibly by interfering with the release of vasoconstrictor transmitters, and neurogenic NO also inhibits the contraction postjunctionally by physiological antagonism.

Origin of innervation in the feline ophthalmic artery.

In this study, we investigate the innervation to the feline ophthalmic artery by the horseradish peroxidase (HRP) tracing method. Five adult cats with body weights ranging between 2.0 and 3.0 kg were used. Under microscopic dissection, the ophthalmic artery was identified and isolated. A gelfoam (Upjohn Co.), 1 x 3 mm in size, containing 0.1 ml of HRP was applied to the prepared artery segment for 2 h. The cat was sacrificed 3 days later. The trigeminal, stellate, superior cervical, middle cervical and nodal ganglia, and oculomotor, trochlear and abducens nuclei were removed, sectioned and stained for HRP-positive cells. HRP-labeled neurons were found in the ipsilateral trigeminal (TRG) and superior cervical ganglia (SCG). The middle cervical, stellate, Edinger-Westphal, trochlear and abducens nuclei were all deemed negative for HRP-labeled cells. In the TRG, HRP-labeled neurons ranged from 21 to 250 (mean +/- SE = 93.8 +/- 42.5/ganglion). The labeled neurons were distributed primarily in the ophthalmic branch. In the SCG, the HRP-labeled neurons were distributed evenly in the ganglion, ranging from 6 to 180 (mean +/- SE = 91.6 +/- 31.5/ganglion). Two additional cats having received a sham operation revealed a negative finding. The feline ophthalmic artery is innervated by the ipsilateral TRG and SCG. Such innervation may play a role in regulating blood flow to the optic nerve.

Effect of hyperbaric oxygen on ophthalmic artery blood velocity in patients with diabetic neuropathy.

To assess the relationship between blood flow and the complications of diabetes mellitus, we investigated the changes in the velocity of blood flow in the ophthalmic artery before and after hyperbaric oxygen therapy (HBO), one of the treatments for diabetic neuropathy. Color Doppler imaging was used before and after HBO. Seven diabetic neuropathy patients, 3 diabetics without neuropathy, and 7 normal, control subjects were enrolled. The patients were subjected to breathing 100% oxygen at 2.0 atmosphere absolute (ATA) for 1 hour. Hyperbaric oxygen therapy resulted in an average decrease in blood velocity by 15.0 +/- 9.0% (mean +/- SD) in normal subjects and 10.7 +/- 8.6% in diabetics without neuropathy. Blood velocity returned to the baseline level 4 hours after discontinuation of HBO. In contrast, blood velocity increased by 20.6 +/- 9.5% in diabetic patients with neuropathy irregardless of the severity of the diabetic retinopathy. The resistance index of the ophthalmic artery was not changed during HBO in the group with diabetic neuropathy, indicating that other mechanisms may be implicated, leading to the compensatory changes of blood flow. These results suggest that the increase in the blood velocity in the ophthalmic artery after HBO in diabetic neuropathy patients could be attributed to an imbalance in autonomic nervous function.

Vasoactive intestinal peptide- and nitric oxide synthase-containing nerve fibers in the rat ophthalmic artery have different origins.

BACKGROUND: Neuropeptides are important in the regulation of vascular functions. The purpose of the present study was to investigate the distribution of perivascular nerve fibers containing neuropeptides and nitric oxide synthase (NOS) in the rat ophthalmic artery. METHODS: Neuropeptide- and NOS-containing nerve fibers in the rat ophthalmic artery were identified using immunocytochemistry following unilateral parasympathectomy (electrocoagulation of the sphenopalatine ganglion) and sympathectomy (superior cervical ganglionectomy). The contralateral artery was used as control. RESULTS: Nerve fibers containing vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and NOS were abundant in the wall of the ophthalmic artery. Nerve fibers containing calcitonin gene-related peptide and substance P were scarcer. Following destruction of the sphenopalatine ganglion there was no discernible change in the density of VIP- and NPY-immunoreactive fibers, while the majority of the NOS-containing fibers disappeared. Following sympathectomy the NPY-containing nerve fibers were almost completely eliminated, whereas VIP- and NOS-containing fibers were unaffected. CONCLUSION: The present study demonstrates that the sphenopalatine ganglion is the main contributor of NOS-containing nerve fibers to the rat ophthalmic artery. In contrast, this ganglion apparently is of little importance as a source of VIP-immunoreactive nerve fibers to the artery, demonstrating different origins of the majority of the VIP-and NOS-containing fibers to this artery. The NPY-containing nerve fibers in the rat ophthalmic artery emanate mainly from the superior cervical ganglion.

Functional role of nerve-derived nitric oxide in isolated dog ophthalmic arteries.

PURPOSE: To determine if nitric oxide (NO) is involved in the relaxant response to nerve stimulation by nicotine and electrical pulses in dog external ophthalmic arteries (EOA) and internal ophthalmic arteries (IOA). METHODS: Changes in isometric tension were recorded in helical strips of the arteries, and the presence of perivascular nerve containing NADPH diaphorase was histochemically demonstrated. RESULTS: Nicotine (10(-4) M, EOA and IOA) and transmural electrical stimulation (5 Hz, EOA) produced a slight or no contraction followed by a moderate relaxation in the strips contracted with prostaglandin F2 alpha. The contraction was abolished by alpha-adrenoceptor antagonists. The relaxation was abolished and the contraction was potentiated by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the relaxation was reversed by L-arginine. Contractile response in L-NA-treated EOA was greater than in the IOA, and the relaxation was less in nontreated EOA. NO-induced relaxation and norepinephrine-induced contraction were not influenced by L-NA. There were plenty of nerve fibers visualized by NADPH diaphorase staining method in the adventitia of EOA and IOA, indicating the presence of NO synthase-containing nerves. CONCLUSIONS: The neurogenic relaxation appears to be mediated by NO released from the vasodilator nerve in EOA and IOA. There is a reciprocal innervation in vasodilator nitroxidergic and vasoconstrictor noradrenergic nerves; functionally, the latter is more predominant in EOA than in IOA.

Functional innervation of bovine ophthalmic artery.

To investigate the functional innervation pattern in smooth muscle of bovine ophthalmic artery, we studied the effect of electrical stimulation and various drugs on the mechanical responses of this muscle using isometric tension recording methods. Electrical stimulation evoked phasic contractions which were abolished by guanethidine and tetrodotoxin (TTX), suggesting that the responses were neurogenic in origin. Phentolamine (10(-5) M) and 10(-5) M timolol did not affect this contractions, but 10(-5) M phentolamine and 10(-6) M prazosin markedly reduced the amplitude of contraction evoked by exogenously applied phenylephrine (10(-5) M). Electrical stimulation applied during sustained contraction evoked by 5-hydroxytryptamine in the presence of guanethidine and atropine evoked relaxation which was markedly suppressed by TTX. These results indicate that bovine ophthalmic artery is innervated by adrenergic nerve fibers, and an unidentified neurotransmitter, other than noradrenaline, may play an important role in the excitatory neuroeffector transmission, and that the tissue is also innervated by non-adrenergic non-cholinergic inhibitory nerve fibers.

Sympathetic hyperinnervation protects vascular smooth muscle cells from necrosis in stroke-prone spontaneously hypertensive rats.

Sympathetic nerve fiber distribution and vascular smooth muscle morphology were investigated in the ophthalmic artery of stroke-prone spontaneously hypertensive rats (SHRSP) and were compared with those of normotensive Wistar Kyoto (WKY) rats at the age of 120 days. The distribution of fluorescent noradrenergic (NA) nerve fibers was examined by the glyoxylic acid method. The ophthalmic artery was divided into two portions according to the size of the outer diameter, that is into a proximal portion (above 100 microns) and a distal portion (30-70 microns). The distribution densities of noradrenergic nerve fibers were measured by quantitative image analysis using the Interactive Bild-Analyse System (IBAS). The distribution densities of NA nerve fibers in both portions of the ophthalmic artery were significantly higher (p < 0.01) in SHRSP than that in WKY rats. The difference in the density of NA fibers of the ophthalmic arteries between SHRSP and WKY rats was 1.9 times in the proximal portion and 1.5 times in the distal portion. The vascular smooth muscle cells of the ophthalmic arteries in SHRSP were observed by scanning electron microscope to examine the trophic effect of NA nerve fibers on the vascular smooth muscle cells. The smooth muscle cells of both portions of the ophthalmic arteries in SHRSP showed a smooth surface texture and no necrosis, and were very similar to those of WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Pigment-containing cells in extraocular tissues of the primate.

In the present study pigment-containing (PC) cells, localized in extraocular tissues of man and the cynomolgus monkey, were investigated to establish their localization, nature and relationships with the autonomic nervous system. In the orbit of man as well as the cynomolgus monkey three localizations of PC cells were detected: (1) Tenon's capsule along the ciliary arteries at the level of the entrance of the arteries into the eyeball, (2) Tenon's capsule along the ciliary nerves at the level of the entrance into the eyeball, and (3) the sclera around the ciliary arteries and nerves. Moreover in the orbit of the cynomolgus monkey PC cells were found along and around the accessory lateral rectus muscle. Histological, histochemical and electron microscopical studies led to the conclusions that PC cells are similar in nature to melanocytes and do not have neuronal properties. In contrast to the melanocytes in the anterior segment of the eye in both man and monkey, melanocytes in the extraocular tissues are not innervated either adrenergically or cholinergically.

Vascular responsiveness to periarterial electrical nerve stimulation on canine ophthalmic arteries.

Both periarterial electrical stimulation (ES) and intraluminal application of norepinephrine (NE) produced a vasoconstriction in the isolated canine ophthalmic artery (OA). The ES-induced vasoconstrictor response was markedly inhibited by treatment with tetrodotoxin and slightly but significantly depressed by xylazine, a selective alpha-2 adrenoceptor agonist. Moreover, the ES-induced response was enhanced by either DG-5128, a selective alpha-2 adrenoceptor antagonist, or angiotensin II. The inhibitory effect of bunazosin on the ES-induced response was significant, but it was rather small compared with that on the NE-induced response. The NE-induced constriction was not affected by xylazine and DG-5128, but significantly enhanced by angiotensin II. These results indicate that (1) the ES-induced response is mediated via sympathetic nerve activation, (2) there are inhibitory prejunctional alpha-2 adrenoceptors, (3) there are more postjunctional alpha-1 than postjunctional alpha-2 adrenoceptors in canine OAs, and (4) prejunctional angiotensin II receptors may exist in isolated OA preparations.

Pathways of sympathetic innervation to the superior and inferior (Müller's) tarsal muscles.

Fluorescent staining and fluorescent microscopy were used to evaluate the pathways which the sympathetic nerves followed to reach the smooth muscles of the eyelids. Selected structures from fresh orbits were removed, sectioned, and fluorescently stained utilizing glyoxylic acid. Photographic results from the fresh orbits showed fluorescence accompanying the oculomotor, trochlear, and abducent nerves and branches of the ophthalmic division of the trigeminal (lacrimal, supraorbital, and nasociliary) nerves. The eyelids exhibited intense fluorescence within the tarsus and throughout adjacent connective tissue. The principal paths of the sympathetic nerves are the sensory (first dimension of the trigeminal) and the motor nerves to the orbit. The arteries (in contrast to previous descriptions) do not appear to be a major pathway.