Acute amitriptyline effects on parasympathetic-evoked rat saliva

The present study was undertaken to investigate the acute effects of amitriptyline on salivary secretion evoked by electrical stimulation of the parasympathetic innervations of rat salivary glands. Single intravenous injections of amitriptyline (0.1-1 mg/kg) caused a dose-related decrease in flow and Na concentration of saliva from both parotid and submandibular glands. However, the only effect on K concentration was a slight increase when the salivary flow was almost completely inhibited. Amitriptyline increased the Ca concentration of nerve-evoked submandibular saliva, but had no effect on the Ca concentration of similarly evoked parotid saliva. However, amitriptyline (0.5 and 1 mg/kg) increased the protein concentration of both kinds of saliva. Amylase activity of parotid saliva was also moderately increased by amitriptyline. These effects were similar to those observed with atropine, a known cholinergic receptor antagonist. These results suggest that amitriptyline, like atropine, reduces parasympathetic-evoked salivary secretion by blocking cholinergic receptors.     

Effects of chronic amitriptyline administration on saliva from the parotid and submandibular glands of the rat

The effect of prolonged treatment with amitriptyline on the secretory activity of rat salivary glands evoked by parasympathetic nerve stimulation and isoprenaline administration has been studied. Low doses of amitriptyline (10 mg/kg per day for 2 or 4 weeks), did not significantly affect salivary flow evoked by either parasympathetic nerve or isoprenaline stimulation. Higher doses of amitriptyline (50 mg/kg/day for 2 or 4 weeks) however, markedly decreased parasympathetic-evoked salivary secretion (flow and volume) from both parotid and submandibular glands, while isoprenaline-evoked secretions were unaffected. Sodium, potassium, and calcium concentrations of nerve-elicited or isoprenaline-evoked saliva were not significantly altered by amitriptyline treatment. Protein concentration and amylase activity of nerve-elicited parotid saliva were, however, greatly increased by chronic amitriptyline administration. Possible mechanisms for drug-induced increase in nerveelicited salivary protein concentration include changes in cholinergic receptor binding, release of neuropeptides and variations in phosphatidylinositol turnover, which need further study.     

Effects of sympathetic nerve stimulation in the presence of specific adrenergic antagonists on Na, K, and Cl transport in perfused rat submandibular duct

The role of beta 1- and beta 2-adrenoceptors in the modification of Na, K, and Cl transport in submandibular main duct of rat perfused with bicarbonate saline solution was studied with direct sympathetic nerve stimulation (4 V, 5 ms, 20 Hz) in the presence of specific adrenergic antagonists. Nerve stimulation in the presence of phenoxybenzamine (3 mg/kg b. wt., i.p.) and butoxamine (3 mg/kg b. w.t., i.p.) enhanced Na (44%) and Cl (35%) absorption but inhibited K (24%) secretion. On the other hand, the nerve-evoked response in the presence of phenoxybenzamine and metoprolol (3 mg/kg b. wt., i.p.) decreased K (19%) secretion without any changes in Na and Cl absorption. Therefore, the data suggest that beta 1- and beta 2-adrenoceptors may be present in the duct cells and activation of these receptors can modify electrolyte transport. Furthermore, prior administration of phenoxybenzamine, butoxamine, and metoprolol suppressed the effects of sympathetic nerve stimulation on transductal fluxes of Na, K and Cl; this indicates that the dosages of antagonists used were sufficiently high to block a nerve-evoked response.     

Studies of muscarinic receptor subtypes in salivary gland function in anaesthetized rats

The in vivo study aimed to examine whether muscarinic receptor subtypes other than muscarinic M3 receptors exert exocrine functional roles in the rat salivary glands. The effects of pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were examined on secretion from the major salivary glands evoked by acetylcholine (0.001-10 micromol kg(-1) i.v.) in pentobarbitone-anaesthetized rats. Observations were occasionally made on glandular blood flow. 4-DAMP (0.1-100 nmol kg(-1) i.v.) markedly and equipotently inhibited the acetylcholine-evoked fluid responses in all glands. Pirenzepine (0.1 micromol kg(-1) i.v.-10 mmol kg(-1) i.v.) showed significantly lower inhibitory potency than 4-DAMP, most conspicuously in the parotid, while methoctramine (0.1 micromol kg(-1) i.v.-10 mmol kg(-1) i.v.) exerted an even lesser inhibitory effect. Also against acetylcholine-evoked blood flow increases, 4-DAMP showed a conspicuous potency. At 1 and 10 micromol kg(-1) i.v. of pirenzepine, the antagonist reduced the protein concentration in the submandibular saliva, but not in the parotid saliva. While 4-DAMP (1 and 10 nmol kg(-1) i.v.) significantly inhibited acetylcholine-evoked protein secretory responses in the submandibular glands, methoctramine (below 10 micromol kg(-1) i.v.) affected the responses in neither gland. The reduction of the protein concentration in submandibular saliva caused by 4-DAMP and pirenzepine was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg(-1) i.p.), while L-NAME had no or only minute effects on the parotid protein secretion. Thus, in addition to muscarinic M3 receptors, other muscarinic receptors contribute to in vivo functional responses in rat submandibular and sublingual glands. While these other receptors are muscarinic M1 receptors in the sublingual gland, they may be a different subtype, possibly muscarinic M5 receptors, in the submandibular gland. However, muscarinic M1 receptors may induce indirect effects via nitric oxide in the submandibular gland.     

Beta-adrenergic receptors and cAMP levels of rat parotid and submandibular glands during chronic isoproterenol treatment

The number of cell surface beta-adrenergic receptors and the level of cyclic AMP of the parotid and the submandibular gland were examined in rats treated for up to 10 days with twice daily injections of the beta-adrenergic agonist, isoproterenol. Receptor densities of 125 +/- 8.7 fmol/mg membrane protein for the parotid and 60.1 +/- 5.6 fmol/mg for the submandibular glands were found with [3H]dihydroalprenolol (beta-adrenergic receptor antagonist) binding of glands from control rats. No change from levels of controls was found in the number of beta-receptors of the submandibular gland with chronic isoproterenol stimulation; the parotid glands, on the other hand, showed a 22% decrease in dihydroalprenolol binding from the 4th until the 8th day of treatment. By day 10 of isoproterenol treatment the parotid gland demonstrated a shift from a population consisting of primarily beta-adrenergic receptors to one consisting of equal numbers of beta 1- and beta 2-adrenoceptors. The basal level of cAMP present in cell lysates remained unchanged in the isoproterenol-treated submandibular gland while the parotid gland showed a 30-40% decrease. Control and isoproterenol-treated animals demonstrated the same time course of cAMP accumulation after a single challenge with isoproterenol.     

Sympathetic and parasympathetic interaction in vascular and secretory control of salivary glands in anaesthetised dogs

The present study was undertaken to examine sympathetic-parasympathetic interactions in the regulation of salivary gland function, with special reference to the possible role of the sympathetic cotransmitter neuropeptide Y (NPY). In dogs anaesthetised with pentobarbitone, electrical stimulation of the parasympathetic nerve to the submandibular gland evoked an increase in glandular blood flow and salivary secretion. Sympathetic nerve stimulation evoked a significant prolonged attenuation of vasodilator and secretory responses to subsequent parasympathetic stimulation. This attenuation was not significantly altered by alpha- and beta-adrenoceptor blockade. Systemic administration of the sympathetic cotransmitter, NPY, mimicked the effect of the sympathetic stimulation by significantly attenuating vasodilatation and salivary secretion. The NPY Y1 receptor agonist, [Leu31, Pro34]NPY and the specific NPY Y2 receptor agonist N-acetyl[Leu28, Leu31]NPY 24-36 both significantly attenuated the vasodilatation and salivary secretion evoked by stimulation of the parasympathetic nerve. The NPY Y1 receptor antagonist, GR231118 significantly antagonised the attenuation of vasodilatation caused by both sympathetic stimulation and the NPY Y1 receptor agonist. GR231118 also inhibited the pressor response of NPY. Intra-arterial injection of methacholine and stimulation of the parasympathetic nerve both caused local vasodilatation in the gland which was significantly attenuated by pretreatment with sympathetic stimulation or the NPY Y1 agonist. The NPY Y2-specific agonist did not attenuate methacholine-induced vasodilatation but did attenuate vasodilatation evoked by parasympathetic stimulation. The results indicate that NPY as a sympathetic cotransmitter may have a role in the regulation of vascular secretory function of salivary glands.     

Regions in the brainstem and frontal cortex where electrical stimulation elicits parotid and submandibular saliva secretion in sheep

Acute experiments were conducted in sheep anaesthetized with sodium pentobarbital to identify regions in the brain where electrical stimulation would elicit secretion by the parotid and submandibular salivary glands. This was a prerequisite for single unit studies in the future. In the brainstem, parotid and submandibular secretions were evoked on average between 7 and 16 mm rostral to obex and from 1 to 11 mm lateral to midline, with the parotid gland being active on the caudal and the submandibular on the rostral sides of this region. Overlap of the two sites was common. The combined region was either between cranial nerves VII and IX or adjacent to either one of them. Stimulating the caudal edge of the parotid sites evoked relatively high parotid secretion rates compared with other areas whereas secretions were uniform throughout the submandibular sites. The combined sites were from 2 to 5 mm deep, the dorsal edge being 1 mm below the floor of the fourth ventricle near midline and 6 mm below it at the lateral extremes. From a dorsal perspective, their orientation was essentially in the lateral plane except that the submandibular site angled slightly rostrally from midline. Profuse parotid secretion was also consistently evoked by stimulating the frontal cortex 15-20 mm from midline and 0-15 mm under the apex. Weak submandibular responses were observed in about half of the sheep. There were no effects on either gland of stimulating the olfactory bulbs. This is the first report of the regions in the brain which increase parotid and submandibular saliva secretion in ruminants. The three-dimensional representation of both sites in the brainstem of individual animals is more precise than the composite representations published to date for other species.     

External radiation of the parotid glands significantly reduces drooling in patients with motor neurone disease with bulbar paresis.

The parotid glands and part of the submandibular glands were irradiated in 18 amyotrophic lateral sclerosis patients with very advanced disease and severe drooling problems. In a prospective study, a single dosage of 7.0-7.5 Gy was administered bilateral to the larger part of the parotid glands and the posterior parts of the submandibular glands. Salivary secretion rate was assayed before and after radiotherapy. Sixteen out of eighteen patients reported satisfactory to good reduction in drooling lasting up to 4-6 months, 1/18 developed xerostomia and needed saliva substitutes, and 1/18 reported no effect. Caregivers reported positive effect in all patients. The procedure was well tolerated with few side effects. Low dosage external radiotherapy of the salivary glands is effective in reducing drooling satisfactorily in ALS patients, especially in well-hydrated patients.     

Effect of salivation on neural taste responses in freely moving rats: analyses of salivary secretion and taste responses of the chorda tympani nerve

The outer surface of the mammalian taste receptor cell is usually covered with saliva, which may affect the initial process of gustation. To ascertain the interaction between salivation and gustation, salivary secretion from the submandibular and parotid glands and taste responses of the chorda tympani nerve were analyzed in the rat, during grooming, eating, and licking of the four standard taste stimuli (sucrose, NaCl, HCl, and quinine hydrochloride). Regions of the tongue surface bathed by saliva secreted from the each gland were examined, and it was found that: (1) Rats frequently groomed, and the anterior part of the tongue, innervated by the chorda tympani nerve, was usually covered with a mixture of submandibular saliva and substances on the body surface. (2) Licking of acceptable sucrose and NaCl solutions elicited initial phasic and long-lasting tonic taste responses, and did not evoked saliva enough to wash away the stimuli from the oral cavity. Licking of rejectable quinine evoked only a small phasic taste response and was followed by taste rejection behavior, accompanied by maximum salivation which could wash out the stimuli. (3) When taste responses were compared under awake and anesthetized (the tongue adapted to water) condition, sucrose response was larger, while responses to other taste stimuli were smaller under the awake condition. Rise time of the phasic NaCl response was longer under the awake condition. These taste response alterations may reflect the effects of prolonged adaptation of the tongue to the mixture of submandibular saliva and body surface substances, and flow rate of licked taste stimuli on the tongue surface.     

Calcium and norepinephrine levels of rat salivary glands after terbutaline, dobutamine or isoproterenol

Present data show that a dose-related increase in calcium concentration [Ca] of submandibular glands of rat occurred after 6 days of twice daily administration of 25, 50 or 75 mg/kg b. wt. doses of the beta 1-adrenergic agonist, dobutamine, or the beta 2-adrenergic agonist, terbutaline. The beta 1-adrenergic receptor was responsible for mediation of these changes with both agonists since the effects of either agonist were prevented when a 10 mg/kg dose of the beta 1-antagonist, atenolol, was injected 20 min prior to the agonist, and the increase induced by either agonist was not prevented when the beta 1-adrenergic antagonist, butoxamine, was given prior to each agonist. Dobutamine caused more marked increases in [Ca] than did terbutaline. The parotid gland, however, showed a decrease with both agonists, and that caused by dobutamine was greater than that caused by terbutaline. Neither antagonist had any effect on the agonist-induced changes in the parotid gland. Reasons for the differences in response of the two glands are suggested. It does not appear, however, that, as suggested previously, the increase in the [Ca] of the submandibular gland is dependent on depletion of glandular levels of norepinephrine (NE). Of the agonists, only dobutamine caused a decrease in glandular concentration of NE, as well as total NE of the gland. With isoproterenol (ISO), NE concentration of parotid and submandibular was reduced, but with terbutaline only that of parotid was reduced. changes in total glandular NE were not found in either gland with either ISO or terbutaline. Thus, the decrease in concentration was a consequence of the increased mass of gland. With cyclocytidine (CC), both NE concentration and total NE were reduced, even though gland size increased. With reserpine (RES), NE concentration as well as total NE were markedly reduced (87-90%), and no change in gland size occurred. It is suggested, on the basis of present data, that prolonged activation of beta 1-adrenoceptors is the cause of the calcium accumulation, and that reduction in NE is not the cause of the calcium increase, but may only be a coincident event. Even with sympathectomy (here induced by reserpine), activation of beta-receptors over a long period of time is suggested as the cause of the calcium change, not the depletion of NE. The present data also provide the first evidence that CC causes NE depletion.     

Noradrenergic modulation of glutamate release in the cerebellum

The effect of alpha- and beta-adrenergic agonists has been studied on the release of newly synthesized [3H]glutamate and [3H]GABA from slices of rat cerebellum. The beta 2-adrenergic agonist salbutamol, and also noradrenaline in the presence of the alpha-adrenergic antagonist phentolamine, both potentiated the K+-evoked release of [3H]glutamate. This potentiation appears to be mediated by adenylate cyclase activation. No effects of beta-adrenergic stimulation were observed on [3H]GABA release. The alpha-adrenergic agonist clonidine inhibited both the [3H]glutamate and the [3H]GABA release evoked by K+. The results suggest that noradrenergic modulation of cerebellar activity may have a presynaptic as well as postsynaptic origin.     

Autonomic control of protein production by the parotid gland of the sheep

The role of adrenoceptors in the control of parotid salivary function has been investigated in anaesthetized sheep. The enhancement of parotid protein output that occurs when the parasympathetic and sympathetic innervations to the gland are stimulated simultaneously in bursts at a low frequency (20 Hz for 1 s at 10-s intervals) was effectively abolished by pretreatment with propranolol (> or = 1.0 mg kg(-1), i.v., P < 0.001), without a comparable reduction in the flow of saliva or in the output of sodium or potassium. Secretion of protein was similarly augmented by simultaneous stimulation of the sympathetic innervation and an intracarotid infusion of acetylcholine (0.4-0.6 microg min(-1) g gland(-1)). This effect was also abolished by pretreatment with propranolol. Pretreatment with phentolamine (>1.0 mg kg(-1), i.v.) had no effect on the output of protein that occurred during combined stimulation of the parasympathetic and sympathetic innervations but increased the flow of saliva and the output of electrolytes. Stimulation of the parasympathetic innervation to the parotid gland caused a substantial fall in vascular resistance, which was reduced by the administration of atropine (0.5 mg kg(-1)). Stimulation of the sympathetic innervation caused a substantial rise in parotid vascular resistance in atropinized sheep. This effect was greater during continuous stimulation than during intermittent stimulation and enhanced by pretreatment with propranolol. It was virtually eliminated by pretreatment with phentolamine. It is concluded that the enhancement of protein output from the ovine parotid gland, that occurs during combined stimulation of the parasympathetic and sympathetic innervations at relatively low frequencies, depends upon interaction between cholinergic muscarinic and beta-adrenergic receptors. The vasoconstriction that occurs during sympathetic stimulation alone can be accounted for by activation of alpha-adrenoceptors.     

The effect of chorda tympani section on ipsilateral and contralateral salivary secretion and taste in man.

Bilateral chorda tympani section is an accepted treatment for troublesome sialorrhoea. Nevertheless the effects of this operation have been poorly studied. Twenty patients were studied with unilateral chorda tympani section and a healthy contralateral ear. The effects on ipsilateral and contralateral stimulated submandibular and parotid flow and taste recognition and detection thresholds were measured. Stimulated submandibular flow accounted for only 27% of the total salivary flow. Chorda tympani section had no effect on submandibular flow in seven patients and only reduced submandibular flow by approximately 54% in the remaining 13 patients. No significant effect was observed on ipsilateral parotid flow rate. Electrogustometric taste detection thresholds were more than twice the accepted upper limit of normal on the lesioned side and taste recognition thresholds were also markedly abnormal. Chorda tympani section alone is a poor method of reducing stimulated salivary flow.     

Inhibitory effects of atropine and adrenergic antagonists on the changes in autonomic receptors and cyclic nucleotides of rat parotid and submandibular glands caused by sympathetic nerve stimulation

The changes in cyclic AMP (cAMP) concentration and density of beta-adrenoceptors caused by electrical stimulation of the sympathetic innervation to parotid and submandibular glands of rat did not occur when the alpha- and beta-adrenergic antagonists, phentolamine, and propranolol were administered 20 min prior to initiation of stimulation. They also did not occur when phentolamine, the beta-adrenergic antagonist, was administered alone prior to nerve stimulation, indicating that beta-adrenoceptors mediate these effects. Simultaneous administration of the alpha- and beta-antagonists also prevented the changes in densities of muscarinic receptors and cGMP concentrations usually induced by sympathetic nerve stimulation. Also, the changes in muscarinic receptors and cGMP did not occur when atropine was administered prior to nerve stimulation, nor did they occur with simultaneous administration of atropine, phentolamine + propranolol; with phentolamine alone, or propranolol alone, the effects were blocked to a large extent. Secretion was inhibited completely when both adrenergic antagonists were present during nerve stimulation, but flow rate was unchanged when atropine was present. The changes in both beta-adrenoceptors and muscarinic receptors reflect a desensitization caused by prolonged exposure to neurotransmitters released when the sympathetic nerve is stimulated. The changes are prevented when either atropine or adrenergic antagonists are present during nerve stimulation.     

Botulinum toxin type A on oral health in treating sialorrhea in children with cerebral palsy: a randomized, double-blind, placebo-controlled study

Intrasalivary gland injection of botulinum toxin type A is known to treat sialorrhea effectively in children with cerebral palsy. However, oral health may be compromised with escalating dose. In this randomized, double-blind, and placebo-controlled pilot trial, the authors aim to determine the therapeutic effect of low-dose, ultrasonography-controlled botulinum toxin type A injection to bilateral parotid and submandibular glands on oral health in the management of sialorrhea. Twenty children diagnosed with cerebral palsy were randomly assigned to 2 groups. The treatment group received botulinum toxin type A injections, whereas the control received normal saline in the same locations. The authors evaluated subjective drooling scales, salivary flow rate, and oral health (salivary compositions and cariogenic bacterial counts). A significant decrease was found in salivary flow rate at the 1- and 3-month follow-up in the botulinum toxin-treated group. The authors suggest that current protocol can effectively manage sialorrhea while maintaining oral health.     

Individually Modified Saliva Delivery Changes the Perceived Intensity of Saltiness and Sourness

Individuals vary largely in their salivary flow and composition, and given the importance of saliva on perception of taste, this might influence how the tastant stimuli are perceived. We therefore hypothesise that altering the individual salivary flow rates has an impact on the perceived taste intensity. In this study, we investigated the role of saliva amount on the perceived taste intensity by excluding parotid saliva and adding artificial saliva close to the parotid duct at preset flow rates. Significant decreases in perception with increasing salivary flow rates were observed for citric acid and sodium chloride. This can partially be explained by a dilution effect which is in line with previous studies on detectable concentration differences. However, since the bitterness and sweetness remained unaffected by the salivary flow conditions and the dilution effect was comparable to that of saltiness, further explanation is needed. Furthermore, we investigated whether the suppression of taste intensity in binary mixtures (taste-taste interactions) could possibly be caused by the increased salivary flow rate induced by an additional taste attribute. The results show, however, that suppression of taste intensity in binary mixtures was not affected by the rate of salivation. This was more likely to be explained by psychophysics.     

超声定位肌电图引导下A型肉毒毒素治疗重度流涎的临床观察

目的：评价A型肉毒毒素（BTX-A）治疗流涎的疗效。方法：选择流涎患者5例,其中帕金森病（PD）3例,脑梗死2例。采用教师流涎分级法（TDS）及流涎频率评分后于超声定位后肌电图引导下对患者腮腺和颌下腺进行BTX-A多点注射,于治疗前及治疗后2周、1个月和3个月时进行流涎测评。结果：TDS和流涎频率评分：BTX-A治疗前为（4.6±0.5）分和（3.0±0.0）分;BTX-A注射后2周降至（2.6±0.9）分和（1.6±0.5）分;1个月时为（2.8±1.1）分和（1.8±0.8）分,与治疗前比,差异有统计学意义（P〈0.05）;3个月时为（3.2±1.3）分和（2.0±1.0）分,与治疗前比,差异仍有统计学意义（P〈0.05）。5例患者均无明显并发症出现。结论：BTX-A局部注射治疗流涎是一种安全、有效的新方法。     

Effects of Different Tastants on Parotid Saliva Flow and Composition

Saliva from parotid glands plays a role in taste perception. Parotid saliva is also stimulated by tastants. The aim of this work is to investigate the effects of different tastants on the parotid salivary response in six subjects. Five tastants were given in different concentrations in solution and held in the mouth for 10 s. The flow rate, protein concentration, and pH of secreted parotid saliva were monitored continuously for 5 min. Stimulation by tastants on flow rate response consists of an immediate rise in flow followed by a plateau and a rapid return to prestimulus flow. Response of pH results in a slower increase while protein concentration consists in a slower decrease, both followed by a return to prestimulus levels in about 4 min. From a resting flow rate of about 140?μL/min, an increase in flow rate to 370?μL/min was caused by stimulation for 10 s with 10 mL of solutions of 0.01 M citric acid, 0.13 M MgSO₄, 0.25 M monosodium glutamate, 0.5 M NaCl, or 0.5 M sucrose. Comparisons of the different tastants showed that the pH of stimulated parotid saliva increased linearly (r?=?0.9), irrespective of the nature of the tastant. Protein concentration decreased (r?=??0.45) and protein amount increases (r?=?0.58) with increase in flow rate for all tastants. Corrected for the effects of flow rate, protein amount depended on the nature of the tastant with the greatest secretion after stimulation by citric acid. Flow rate was largely responsible for pH but tastant appears to play an additional role with flow rate on protein secretion.     

Salivary and lacrimal secretions in patients on lithium therapy

Salivary and lacrimal secretion rates and salivary composition were examined in 22 manic-depressive patients on lithium therapy and in 21 matched, healthy controls. Serum immunoglobulins (IgG and IgA) were measured in these patients. Their oral health was examined and found to be unimpaired. Significantly lowered tear secretion was detected in the patients, while their salivary secretion rates were normal. The salivary concentrations of NA, K and IgA were significantly elevated in whole saliva. In parotid saliva, the concentrations of K and IgA were elevated, while Na was in the normal range. A significant correlation between serum and salivary lithium concentrations was found, indicating the usefulness of salivary measurements for monitoring.Informed consent of the patients was obtained after the nature of the procedures had been fully explained.     

Simultaneous measurement of parasympathetic reflex vasodilator and arterial blood pressure responses in the cat

We measured the changes in lower lip blood flow and systemic arterial blood pressure evoked by lingual nerve or trigeminal spinal nucleus (Vsp) stimulation to gain an insight into the brainstem integration of sympathetic and parasympathetic responses to nociceptive stimulation. We used artificially ventilated, cervically vago-sympathectomized cats deeply anesthetized with alpha-chloralose and urethane. A lip blood flow increase occurred in an intensity- and frequency-dependent manner following electrical stimulation of Vsp or lingual nerve regardless of whether systemic arterial blood pressure increased or decreased. In contrast, there was no apparent optimal frequency for the changes in systemic arterial blood pressure elicited by electrical stimulation of Vsp or lingual nerve. No relationship was found between the amplitude of the lip blood flow increase and that of the systemic arterial blood pressure change. Microinjection of lidocaine or kainic acid into the Vsp evoked, respectively, reversible and irreversible inhibition of the lip blood flow increase and systemic arterial blood pressure change evoked by lingual nerve stimulation. When microinjected unilaterally directly into the ipsilateral Vsp, the GABA agonist muscimol abolished both lingual nerve-evoked effects (increase in lip blood flow and changes in systemic arterial blood pressure) without changing basal systemic arterial blood pressure, suggesting the presence in the Vsp of GABA receptors serving to modulate both the parasympathetically mediated lip blood flow increase and the sympathetically mediated systemic arterial blood pressure change. Lidocaine microinjection into the salivatory nucleus caused a significant attenuation of the lingual nerve-induced blood flow increase, but had no effect on the lingual nerve-induced systemic arterial blood pressure change. Thus, the neural pathway mediating the lingual nerve-induced lip blood flow increase seems to be simple, requiring a minimum of four neurons: trigeminal afferent-Vsp-parasympathetic pre-ganglionic neurons with cell body located in the inferior salivatory nucleus-otic postganglionic neuron. On the other hand, the pathway underlying the evoked systemic arterial blood pressure changes, presumably mediated via altered sympathetic activity, seems to be more complicated and could be affected by more numerous factors.