Parasympathetic Reflex Vasodilatation Research Articles

Effect of the parasympathetic vasodilation on temperature regulation via trigeminal afferents in the orofacial area

The skin temperature (Tm) of the orofacial area influences orofacial functions and is related to the blood flow (BF). Marked increases in BF mediated by parasympathetic vasodilation may be important for orofacial Tm regulation. Therefore, we examined the relationship between parasympathetic reflex vasodilation and orofacial Tm in anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited significant increases in BF and Tm in the lower lip. These increases were significantly reduced by hexamethonium, but not atropine. VIP agonist increased both BF and Tm in the lower lip. The activation of the superior cervical sympathetic trunk (CST) decreased BF and Tm in the lower lip; however, these decreases were significantly inhibited by LN stimulation. Our results suggest that parasympathetic vasodilation plays an important role in the maintaining the hemodynamics and Tm in the orofacial area, and that VIP may be involved in this response.

Parasympathetic reflex vasodilation in the cerebral hemodynamics of rats

We investigated the role of parasympathetic reflex vasodilation in the regulation of the cerebral hemodynamics, and whether GABAA receptors modulate the response. We examined the effects of activation of the parasympathetic fibers through trigeminal afferent inputs on blood flow in the internal carotid artery (ICABF) and the cerebral blood vessels (rCBF) in parietal cortex in urethane-anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases in ICABF that were independent of changes in external carotid artery blood flow. Increases in ICABF were elicited by LN stimulation regardless of the presence or absence of sympathetic innervation. The ICABF increases evoked by LN stimulation were almost abolished by the intravenous administration of hexamethonium (10 mg kg(-1)) and were reduced significantly by atropine administration (0.1 mg kg(-1)). Although the LN stimulation alone had no significant effect on rCBF, LN stimulation in combination with a blocker of the GABAA receptor pentylenetetrazole increased the rCBF markedly. This increase in rCBF was reduced significantly by the administration of hexamethonium and atropine. These observations indicate that the increases in both ICABF and rCBF are evoked by parasympathetic activation via the trigeminal-mediated reflex. The rCBF increase evoked by LN stimulation is thought to be limited by the GABAA receptors in the central nervous system. These results suggest that the parasympathetic reflex vasodilation and its modulation mediated by GABA receptors within synaptic transmission in the brainstem are involved in the regulation of the cerebral hemodynamics during trigeminal afferent inputs.

GABAB receptors in the NTS mediate the inhibitory effect of trigeminal nociceptive inputs on parasympathetic reflex vasodilation in the rat masseter muscle

The present study was designed to examine whether trigeminal nociceptive inputs are involved in the modulation of parasympathetic reflex vasodilation in the jaw muscles. This was accomplished by investigating the effects of noxious stimulation to the orofacial area with capsaicin, and by microinjecting GABA(A) and GABA(B) receptor agonists or antagonists into the nucleus of the solitary tract (NTS), on masseter hemodynamics in urethane-anesthetized rats. Electrical stimulation of the central cut end of the cervical vagus nerve (cVN) in sympathectomized animals bilaterally increased blood flow in the masseter muscle (MBF). Increases in MBF evoked by cVN stimulation were markedly reduced following injection of capsaicin into the anterior tongue in the distribution of the lingual nerve or lower lip, but not when injected into the skin of the dorsum of the foot. Intravenous administration of either phentolamine or propranolol had no effect on the inhibitory effects of capsaicin injection on the increases of MBF evoked by cVN stimulation, which were largely abolished by microinjecting the GABA(B) receptor agonist baclofen into the NTS. Microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS markedly attenuated the capsaicin-induced inhibition of MBF increase evoked by cVN stimulation, while microinjection of the GABA(A) receptor antagonist bicuculline did not. Our results indicate that trigeminal nociceptive inputs inhibit vagal-parasympathetic reflex vasodilation in the masseter muscle and suggest that the activation of GABA(B) rather than GABA(A) receptors underlies the observed inhibition in the NTS.

Role of medullary GABA signal transduction on parasympathetic reflex vasodilatation in the lower lip

In the orofacial area, noxious stimulation of the orofacial structure in the trigeminal region evokes parasympathetic reflex vasodilatation, which occurs via the trigeminal spinal nucleus (Vsp) and the inferior/superior salivatory nucleus (ISN/SSN). However, the neurotransmitter involved in the inhibitory synaptic inputs within these nuclei has never been described. This parasympathetic reflex vasodilatation is suppressed by GABAergic action of volatile anesthetics, such as isoflurane, sevoflurane, and halothane, suggesting that medullary GABAergic mechanism exerts its inhibitory effect on the parasympathetic reflex via an activation of GABA receptors. The aim of the present study was to determine the role of GABAA and GABAB receptors in the Vsp and the ISN in regulating the lingual nerve (LN)-evoked parasympathetic reflex vasodilatation in the lower lip. Under urethane anesthesia (1g/kg), change in lower lip blood flow elicited by electrical stimulation of the LN was recorded in cervically vago-sympathectomized rats. Microinjection of GABA (10μM; 0.3μl/site) into the Vsp or the ISN significantly and reversibly attenuated the LN-evoked parasympathetic reflex vasodilatation. Microinjection of the GABAA receptor-selective agonist muscimol (100μM; 0.3μl/site) or the GABAB receptor-selective agonist baclofen (100μM; 0.3μl/site) into the Vsp or the ISN significantly and irreversibly reduced this reflex vasodilatation, and these effects were attenuated by pretreatment with microinjection of each receptor-selective antagonists [GABAA receptor selective antagonist bicuculline methiodide (1mM; 0.3μl/site) or GABAB receptor selective antagonist CGP-35348 (1mM; 0.3μl/site)] into the Vsp or the ISN. Microinjection of these antagonists alone into the Vsp or the ISN had no significant effect on this reflex vasodilatation. In addition, microinjection (0.3μl/site) of the mixture of muscimol (100μM) and baclofen (100μM) into the Vsp or the ISN also significantly reduced this reflex vasodilatation. These results suggest that medullary GABA signal transduction inhibits the parasympathetic reflex vasodilatation in the rat lower lip via GABAA and GABAB receptors in the Vsp and the ISN.

Parasympathetic reflex vasodilatation in the masseter muscle compensates for carotid hypoperfusion during the vagus-mediated depressor response

Parasympathetic vasodilatation in the orofacial area is thought to be an important factor in the regulation of blood flow in the common carotid artery (CABF), and disturbances in parasympathetic vasodilatations may be related to impairment of the CABF inducing craniofacial ischemia. We hypothesized that the parasympathetic vasodilatation in the masseter muscle evoked by a vagus-mediated reflex is involved in the maintenance of the CABF during the vagus-mediated depressor response. In the present study, we compared changes in blood flow in the masseter muscle (MBF) and CABF, and systemic arterial blood pressure (SABP) evoked by electrical stimulation of the central cut end of the cervical vagus nerve (cVN) in anesthetized and sympathectomized rats. Electrical stimulation of the cVN in the sympathectomized animals caused an increase in MBF followed by a CABF increase, although it simultaneously induced a decrease in SABP. These increases in blood flow changed to decreases after intravenous administration of atropine (100μg/kg), while pretreatment with atropine had no effect on the changes in SABP. Microinjection (50nl/site) of the muscimol (1mM), into the nucleus of the solitary tract, which is involved in reflex cardiovascular regulation, markedly inhibited the cVN stimulation-induced MBF increase. Our results indicate that vagal-parasympathetic vasodilatation in the masseter muscle compensates for carotid hypoperfusion during the vagus-mediated depressor response, and that GABAergic neurons may be involved in the inhibition of this response. This inhibition may result in the impairment of CABF, suggesting an important role in the etiology of neurally mediated syncope.

Vagal visceral inputs to the nucleus of the solitary tract: Involvement in a parasympathetic reflex vasodilator pathway in the rat masseter muscle

The present study examined whether vagal visceral inputs are involved in parasympathetic reflex vasodilatation in the masseter muscle in urethane-anesthetized and cervically sympathectomized rats. Electrical stimulation of the central cut end of the cervical vagus nerve (VN) including visceral afferent fibers, which consisted of cervical/thoracic branches (heart and lungs) and abdominal branches (entire gastrointestinal tract), elicited intensity- and frequency-dependent increases of blood flow in the masseter muscle (MBF). Activation of the abdominal VN inferior to the diaphragm failed to affect the MBF. MBF increases evoked by cervical VN stimulation were reduced significantly by hexamethonium. Pretreatment with atropine reduced the MBF increase evoked by VN stimulation significantly, whereas pretreatment with either propranolol or phentolamine had no effect on the response. MBF increases occurred with electrical stimulation of nucleus of the solitary tract (NTS), and these increases were significantly reduced by the administration of hexamethonium and atropine. MBF increases also occurred after microinjection of glutamate into the NTS in a dose-dependent manner. Microinjection of muscimol into the NTS caused a significant attenuation of the VN stimulation-induced MBF increases. Our results suggest that vagal visceral inputs passing to the NTS are involved in the parasympathetic reflex vasodilatation in the rat masseter muscle. The MBF increase evoked by the vagal-parasympathetic reflex mechanism occurred via visceral afferents running in the cervical VN, but not in the abdominal VN, suggesting that the vagal visceral afferents derived from cardiovascular and/or respiratory systems may play an important role in the regulation of the MBF.

Difference between male and female rats in cholinergic activity of parasympathetic vasodilatation in the masseter muscle

We compared the changes in blood flow of the masseter muscle (MBF), lower lip (LBF) and common carotid artery (CCABF) evoked by electrical stimulation of the lingual nerve (LN) in order to examine whether high cholinergic activity of parasympathetic vasodilatation in females is specific for the masseter muscle, and whether sex-associated differences in cholinergic parasympathetic vasodilatation affect the regulation of blood flow to the orofacial area from the CCABF in urethane-anaesthetized, vago-sympathectomized male and female rats. Increases in the MBF, LBF and CCABF evoked by LN stimulation appear to be mediated via an activation of parasympathetic reflex vasodilatation since these increases were profoundly reduced by pretreatment with the autonomic cholinergic ganglion blocker hexamethonium (10 mg/kg). Although α- and β-adrenoceptor antagonists (phentolamine and propranolol, 100 μg/kg) had no effect on the LN stimulation-induced blood flow increases in either sex, a marked difference was found between males and females in the effects of the antimuscarinic agent atropine (1–100 μg/kg) on these blood flow increases. Pretreatment with atropine slightly attenuated the increase in the MBF in males, but in females it markedly reduced the increases in all three sites measured, especially in the MBF. Our results suggest that (1) cholinergic activity of the parasympathetic vasodilatation in females is higher than that in males in most orofacial tissues, but particularly in the masseter muscle and (2) cholinergic parasympathetic vasodilatations are more involved in the regulation of blood flow to the orofacial area from the CCABF in females than in males.

Effects of Isoflurane on Parasympathetic Vasodilatation in the Rat Submandibular Gland

Volatile anesthetics have been known to suppress parasympathetic reflex vasodilatation in the lower lip and palate. However, in the submandibular gland, little is known about the effects of these anesthetics on the parasympathetic vasodilatation elicited by reflex and direct (i.e., non-reflex) activation of the parasympathetic vasodilator mechanisms. Although both parasympathetic vasodilatations were inhibited by isoflurane in a concentration- and time-dependent manner, the effects of continuous administration of the alpha(1)-adrenoceptor agonist methoxamine were markedly different: The reflex vasodilatation was not affected by methoxamine, while the direct vasodilatation was significantly reduced. Picrotoxin (GABA(A) receptor antagonist) attenuated the inhibitory effect of isoflurane on direct vasodilatation and the systemic arterial blood pressure. These findings suggest that the isoflurane-induced inhibitory effects on direct vasodilatation are produced by a decrease of peripheral vascular tone by GABAergic mechanisms, whereas those on the reflex vasodilatation are produced exclusively by the inhibition of the reflex center.

Parasympathetic Vasodilator Fibers in the Orofacial Region

The present report focuses on a review of A) the parasympathetic vasodilator fibers in the orofacial skin, B) the central mechanism by which trigeminal stimulation elicits parasympathetic reflex vasodilatation, and C) the presence of parasympathetic vasodilator fibers in the jaw muscles. A) The parasympathetic neurons, particularly those running as efferents in the glossopharyngeal nerve, were involved in vasodilatation elicited by stimulation of the infra-orbital nerve and the maxillary buccal gingiva. Furthermore, the vasodilator response was not affected by lesion of the pterygopalatine ganglion, suggesting that reflex vasodilatation is mediated via the otic ganglion but not via the pterygopalatine ganglion. B) The trigeminal spinal nucleus is an important bulbar relay for lingual nerve-evoked parasympathetic reflex vasodilatation in the lower lip. C) There are parasympathetic cholinergic and non-cholinergic vasodilator fibers originating from cell bodies in the otic ganglion in the rat masseter muscle, and that these fibers are reflexly activated by trigeminal afferent nerve stimulation. The physiological function of the parasympathetic vasodilator fibers in the orofacial area is unknown. However, it has recently been suggested that the trigeminal system may participate in autonomic and behavioral functions such as feeding and drinking. The present review adds a new facet to the evidence that there is a close link between parasympathetic vasodilator fibers and the trigeminal system in the facial area.

Bulbar pathway for contralateral lingual nerve-evoked reflex vasodilatation in cat palate

We investigated the brain-stem pathway(s) by which electrical stimulation of the central cut end of the lingual nerve (LN) evokes parasympathetic reflex vasodilatation in the palate contralateral to the stimulated side. This occurs in artificially ventilated, cervically vagosympathectomized cats deeply anesthetized with α-chloralose and urethane. For this purpose, we made microinjections within the brain stem to produce nonselective, reversible local anesthesia (lidocaine) or soma-selective, irreversible neurotoxic damage (kainic acid). Local anesthesia of the trigeminal spinal nucleus (Vsp) ipsilateral to the stimulated side produced by microinjection of lidocaine (2%; 1 μl/site) reversibly and significantly reduced the LN stimulus-evoked palatal blood flow (PBF) increases. PBF increases ipsilateral and contralateral to the stimulated nerve were equally affected. In contrast, microinjection of lidocaine into the Vsp contralateral to the stimulated side did not affect these responses. Microinjection of kainic acid (10 mM/site; 1 μl) into the Vsp ipsilateral to the stimulated side led to a bilateral irreversible reduction in reflex vasodilatation in the palate. Microinjection of lidocaine into either superior salivatory nucleus (SSN) attenuated the PBF increase only on the side ipsilateral to the microinjection site. Hexamethonium (1.0 mg/kg iv) significantly reduced the vasodilator responses to electrical stimulation of Vsp by blocking ganglionic transmission on both sides. The simplest interpretation of these results is that the LN-evoked parasympathetic reflex vasodilatation in the contralateral palate depends on activation of a pathway originating from the Vsp ipsilateral to the stimulated nerve and crossing to the contralateral SSN.

Reduction in parasympathetic reflex vasodilatation following stereotaxic ear-bar insertion: importance of reduced afferent input

As in our previous report, when cats were fitted with stereotaxic ear-bars ‘type A’ animals (26 out of 41) still exhibited a parasympathetic reflex lip blood flow (LBF) increase in response to lingual nerve stimulation, while in ‘type B’ animals (the remaining 15) it was greatly reduced or abolished. We compared (in both magnitude and in their sensitivity to hexamethonium, 10 mg/kg, i.v.) the LBF responses evoked by electrical stimulation of various sites within the reflex arc (lingual nerve, trigeminal ganglion, spinal trigeminal nucleus (Vsp)) in type A and type B animals to examine where the suppressive effect of ear-bar insertion might be exerted (using artificially ventilated, cervically vago-sympathectomized cats deeply anesthetized with α-chloralose and urethane). After ear-bar insertion: (a) in type A animals, stimulation of both lingual nerve and Vsp evoked a similar, hexamethonium-sensitive LBF increase; (b) in type B animals (in which lingual-nerve stimulation evoked no LBF increase), Vsp stimulation evoked a hexamethonium-sensitive LBF increase; (c) in both type A and type B animals, trigeminal ganglion stimulation consistently elicited an LBF increase (abolished by hexamethonium in type A, but reduced by only 50% in type B). These results suggest (i) that abolition of the lingual nerve-induced parasympathetic reflex vasodilatation by ear-bar insertion is due to reduced afferent traffic (in peripheral trigeminal or facial nerves) rather than to a damaged efferent output, and (ii) this effect in type B animals seems somehow to allow an antidromic (hexamethonium-insensitive) vasodilatation to occur on trigeminal ganglion stimulation.

Involvement of trigeminal spinal nucleus in parasympathetic reflex vasodilatation in cat lower lip.

We examined whether the trigeminal spinal nucleus (Vsp) forms part of the central mechanism by which electrical stimulation of the central cut end of the lingual nerve (LN) evokes parasympathetic reflex vasodilatation in the lower lip in artificially ventilated, cervically vagosympathectomized cats deeply anesthetized with alpha-chloralose and urethane. For this purpose, we made microinjections within the brain stem to produce nonselective, reversible local anesthesia (lidocaine) or soma-selective, irreversible neurotoxic damage (kainic acid). Local anesthesia of Vsp by microinjection of lidocaine (2%; 1 microl/site) reversibly and significantly reduced the ipsilateral-LN-evoked parasympathetic reflex vasodilatation. Unilateral microinjection of kainic acid (10 mM/site; 1 microl) into Vsp ipsilateral to the stimulated LN led to an irreversible reduction in the reflex vasodilatation but had no effect on the vasodilatation elicited by stimulation of the contralateral LN. Such microinjection of kainic acid into Vsp had no effect on the vasodilatation evoked by electrical stimulation of the ipsilateral inferior salivatory nucleus. Electrical stimulation of Vsp elicited a blood flow increase in the lower lip in an intensity- and frequency-dependent manner, regardless of whether systemic arterial blood pressure rose or fell. Hexamethonium (1.0 mg/kg iv) significantly reduced the vasodilator responses elicited by electrical stimulation of the central cut end of LN or of Vsp, each to a similar degree. After hexamethonium, both vasodilator responses showed time-dependent recovery. These results strongly suggest that Vsp is an important bulbar relay for LN-evoked parasympathetic reflex vasodilatation in the cat lower lip.

Parasympathetic reflex vasodilatation in rat submandibular gland.

The present study was designed to investigate 1) whether parasympathetic reflex vasodilatation occurs in the submandibular gland (SMG) in deeply urethan-anesthetized, cervically vagotomized, and sympathectomized rats when the central cut end of the lingual nerve (LN) is electrically stimulated and 2) to what extent the neural mechanisms underlying such responses are the same as those involved in the response to direct stimulation of the chorda-LN (CLN). Stimulation of each nerve separately elicited a marked blood flow increase in SMG. Section of the chorda tympani abolished the SMG blood flow response but had no effect on the lip blood flow increase evoked by LN stimulation. Section of the CLN abolished the SMG blood flow increases evoked by stimulation of either nerve. The SMG blood flow increases (regardless of whether they were evoked by LN or CLN stimulation) were markedly reduced by the autonomic cholinergic ganglion blocker hexamethonium. The present study demonstrates that a parasympathetic reflex vasodilator mechanism is present in the rat SMG and that it can express its effects under deep general anesthesia.

Correlation between degree of inhibition of parasympathetic reflex vasodilation and MAC value for various inhalation anesthetics

Parasympathetic reflex vasodilation was elicited in the lower lip by stimulation of the central cut end of the lingual nerve in urethane plus α-chloralose-anesthetized, vago-sympathectomized cats. A dose-related inhibition of this response was induced by the inhalation anesthetics isoflurane, halothane, sevoflurane, and enflurane, the ID 50 values being 0.94%, 0.82%, 1.74%, and 2.0%, respectively. These results indicate that the ID 50 value is approximately two-thirds of the published MAC (for isoflurane, halothane, sevoflurane, and enflurane, 1.6%, 1.2%, 2.6%, and 2.4%, respectively) value for such anesthetics, suggesting that parasympathetic reflex vasodilation is more susceptible than somato-somatic reflexes to inhibition by inhalation anesthetics.

Escape of parasympathetic vasodilatation from sympathetic attenuation in oro-facial areas in the cat.

We examined the effects of concurrent repetitive stimulation of the cervical sympathetic trunk (CST) on the parasympathetically mediated reflex blood flow increase in the orofacial area of cats. In urethane plus alpha-chloralose anaesthetized cats, parasympathetic reflex vasodilatation in the ipsilateral lower lip was elicited by electrical stimulation of the central cut end of the lingual nerve (LN). This blood flow increase was attenuated in a frequency-dependent manner when CST was stimulated concurrently at 0.5-10 Hz for 10 minutes. When we applied repeated LN stimulation (using identical parameters, each time) at intervals during a 30-minutes period of 10 Hz CST stimulation, the attenuation of the blood flow increase gradually weakened in a time-dependent manner even though the direct vasoconstrictor effect of CST stimulation showed no such decline.

Suppression of parasympathetic reflex vasodilatation in the lower lip of the cat by isoflurane, propofol, ketamine and pentobarbital: implications for mechanisms underlying the production of anaesthesia

We have compared the effects of isoflurane, propofol, ketamine and pentobarbital on parasympathetic reflex vasodilatation to investigate their involvement in GABA-mediated synaptic inhibition, enhancement of which is thought to underlie the action of many anaesthetic agents. In cats anaesthetized with urethane-alpha-chloralose, parasympathetic reflex vasodilation in the ipsilateral lower lip was elicited by electrical stimulation of the central cut end of the lingual nerve. Isoflurane and pentobarbital both produced marked dose-dependent inhibition of this vasodilator response. In contrast, propofol and ketamine had no effect on parasympathetic reflex vasodilation. Administration of a GABA antagonist (picrotoxin) reversed the inhibition produced by isoflurane (previous results) and pentobarbital (present study). Our results suggest that isoflurane and pentobarbitone inhibit parasympathetic reflex vasodilatation via a GABA-mediated mechanism, but that propofol and ketamine have no such effect. Our results with propofol cast doubt on its presumed mechanism of action as an anaesthetic.

Effects of inhalation anesthetics on parasympathetic reflex vasodilation in the lower lip and palate of the cat.

The present experiments were designed to examine the effects of inhalation anesthetics (isoflurane, halothane, and sevoflurane) on the parasympathetic reflex vasodilation in the lower lip and palate elicited by electrical stimulation of the central cut end of the lingual nerve in vagosympathectomized cats. Isoflurane (1.5%), halothane (1.0%), and sevoflurane (2.5%), each at a concentration of 1.0 minimum alveolar concentration, markedly suppressed the evoked blood flow increases in the lower lip, whereas nitrous oxide (70% in 30% oxygen) and morphine (2 mg/kg iv) did not. Prior administration of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist (2 mg/kg iv), reversed the inhibitory effect of isoflurane on the parasympathetic reflex response. Decerebration had no significant effect on the isoflurane-induced inhibition. These findings suggest that there is a GABA-mediated suppressive mechanism acting on this parasympathetic reflex response; the sites at which inhalation anesthetics exert such an inhibitory action could be in the midbrain, pons, or medulla, but not in the hypothalamus or higher structure.

Peripheral Action of the Ganglion Blocking Agents

It is generally accepted that the ganglion blocking agents such as tetraethylammonium or hexamethonium has scarcely any peripheral action, but tetraethylammonium exhibits a somewhat stronger acetylcholine-like action on the parasympathetic postganglionic effectors than hexamethonium (1). On the other hand, the vasopressor actions of intravenous adrenaline and some other sympathomimetic amines are greatly increased or prolonged after ganglionic transmission is blocked by these agents (2–4). The explanation on this phenomenon differs from each other. As the effects of these agents on some extirpated organs are almost negligible, Paton and Zaimis, and Moe, concluded that this phenomenon derived from the inactivation of the reflex compensatory haemodynamic mechanism. Page and Taylor considered that the phenomenon caused by tetraethylammonium a result of the release of noradrenaline-like substances from the liver. This potentiation occurs also after vagotomy or full atropinization. Therefore it can not result from the blockade of a parasympathetic reflex vasodilatation.