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Hemodynamic and humoral characteristics of hypertension induced by prolonged stellate ganglion stimulation in conscious dogs.

Recent evidence has suggested that cardiac factors may play a role in the evolution of arterial hypertension. To test the possibility that an increase in cardiac-performance can lead to a sustained increase in systemic blood pressure, we electrically stimulated the left stellate ganglion of six conscious dogs continuously for a 7-day period and monitored cardiac output and arterial blood pressure. In all six dogs, stimulation elicited an abrupt rise in systemic blood pre-sure that was entirely due to rise in cardiac output that lasted at least 6 hours. After 1 day of continuous stimulation, cardiac output retured to control values, but blood pressure remained elevated. After 7 days of stimulation, blood pressure was increased by an average of 25 mm Hg and peripheral resistance by 35 plus and minus 4%. Measurements of blood volume, plasma renin activity, circulating catecholamines (three of the six dogs), and sodium balance showed that none of these factors could explain the development pf this sustained hypertension. Pharmacologic blockade with phenoxybenzamine prevented in large part the rise in blood pressure in short-term stellate ganglion stimulations, whereas propranolol had very little effect on the pressor response, although it nearly abolished the increase in cardiac output. The data indicate that continuous stimulation of the stellate ganglion in conscious dogs leads to substained rises in both blood pressure and peripheral resistance; these changes are apparently mediated by increased activity of the sympathetic nervous system.

Animals↗

Hemodynamic responses to stellate ganglion stimulation in mongrels and greyhounds.

A comparison of the effects of left stellate ganglion stimulation (SGS) on central and aortic hemodynamics has been made in chloralose-anesthetized mongrel (M), and greyhound (GH) dogs. Measurements of aortic pressure and flow, and left ventricular pressure were made during stimulation of the decentralized left SG at different frequencies from 0 to 20 Hz. The increases in aortic pressure and flow with SGS were larger in the GH, especially for low frequencies of stimulation. Stroke volume was increased with SGS in the GH at all stimulation rates, whereas in the M it was unchanged. A greater decrease in left ventricular end-diastolic pressure with SGS was found in the GH. These results suggest that differences exist in both the intrinsic and extrinsic control of cardiac output in the greyhound dog compared to the mongrel. These differences may be in part responsible for the elevated arterial blood pressure in the greyhound compared to the mongrel.

Adrenergic Fibers↗

Effects of unilateral stellate ganglion stimulation and ablation on electrophysiologic changes induced by acute myocardial ischemia in dogs.

We recorded direct-current extracellular electrograms simultaneously from 60 left ventricular epicardial sites in 38 alpha-chloralose-anesthetized dogs during repeated, 5 min coronary arterial occlusions. In each dog recordings made during control occlusions were compared with those made in occlusions after, or during, the following interventions on the sympathetic nervous system: left stellate ganglion stimulation, left stellectomy, right stellectomy, and clamping the abdominal aorta with intact sympathetic nerves to induce a rise of blood pressure equal to that present during left stellate stimulation. Heart rate was kept constant. Measurements included determination of TQ segment potentials and times of local activation. After 2 min of ischemia, the degree of TQ segment depression was increased by left stellate ganglion stimulation and was decreased by both left stellectomy and clamping the aorta. Also, the area showing negative TQ potentials, indicating decreased resting membrane potentials, was enlarged by both left stellate stimulation and right stellectomy and reduced by left stellectomy. No differences were found in the results of experiments in which the left anterior descending coronary artery was occluded and those in which the circumflex branch was occluded. Left stellate stimulation significantly improved conduction within the ischemic zone. No evidence was found to suggest that the arrhythmogenic effects of left stellate stimulation and of right stellectomy, confirmed in the present study, resulted from an increased likelihood for reentry in the subepicardium of the ischemic zone.

Animals↗

Acetylcholine release from guinea-pig ileum by parasympathetic ganglion stimulants and gastrin-like polypeptides.

1. The release of acetylcholine by parasympathetic ganglion stimulants from the nerve terminals of the guinea-pig longitudinal muscle strip was studied. The acetylcholine released was collected in the presence of physostigmine sulphate.2. Nicotine and 1,1-dimethyl-4'-phenylpiperazinium iodide (DMPP) released acetylcholine. Tetrodotoxin (50 ng/ml) and hexamethonium completely prevented their action on acetylcholine release, indicating that their effect is on nicotinic receptors of cell bodies. Noradrenaline (1 mug/ml), excess magnesium, and calcium withdrawal inhibited the acetylcholine release induced by nicotine or by DMPP.3. There was rapid tachyphylaxis to the acetylcholine releasing action of both nicotine and DMPP.4. The octapeptide amide of cholecystokinin and caerulein (10(-9)M) enhanced the acetylcholine release without producing tachyphylaxis. Tetrodotoxin completely inhibited acetylcholine release. However, hexamethonium or desensitization with 5-hydroxytryptamine did not prevent their action. In the early phase of nicotine action the polypeptides studied failed to increase acetylcholine release. However, a few minutes later the tissue became sensitive to polypeptides despite the fact that the tissue was still exposed to nicotine. These data suggest the presence in the parasympathetic ganglion cells of separate gastrointestinal hormone-sensitive receptors.5. Noradrenaline inhibited the acetylcholine releasing action of polypeptides. This effect was mediated via alpha-adrenoceptors since phentolamine prevented its action.6. Excess magnesium (9.3 mM) also reduced the acetylcholine release in response to the polypeptides.

Acetylcholine↗

Intragastric nicotine protection against 40% ethanol injury in rat stomach. Role of ganglionic stimulation or blockade.

Intragastric nicotine (4 mg/kg) protects against 40% ethanol-induced gastric mucosal injury and raises mean blood pressure. We postulated that this protective effect was mediated by the ganglionic stimulatory property of nicotine and therefore could be abolished by ganglionic blockers. Rats were pretreated with intraperitoneal hexamethonium (10 mg/kg) or mecamylamine (2 mg/kg) to block peripheral or central autonomic ganglia, respectively. Intragastric vehicle or nicotine (4 mg/kg) was then administered. The total lengths of the linear gastric corpus mucosal lesions induced by intragastric 40% ethanol were measured by an unbiased observer using a caliper. The results showed that both intraperitoneal hexamethonium and mecamylamine pretreatments protected against 40% ethanol-induced gastric mucosal injury. Neither modified the protective effect of intragastric nicotine. The protective effect of hexamethonium and mecamylamine was associated with a significant increase in the volume of gastric mucus and gastric juice. The increase in the volume of gastric content (mucus and juice) was partially responsible for the protective effect of these ganglionic blockers. In a separate experiment, intraperitoneal nicotine (4 mg/kg) also protected against 40% ethanol-induced gastric mucosal injury and raised mean blood pressure. These data indicate that the protection against 40% ethanol-induced gastric mucosal injury is not unique to intragastric nicotine. Such protection can be induced by ganglionic blocking doses of hexamethonium and mecamylamine, or a ganglionic stimulatory dose of intraperitoneally administered nicotine. Whether ganglionic stimulation or blockade plays a role in the mechanism of intragastric nicotine protection, however, remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of alpha adrenergic blockade during stellate ganglion stimulation on arrhythmias induced by acute myocardial ischemia in pigs.

The effects of alpha-adrenergic receptor blockade during stellate ganglion stimulation on arrhythmias induced by repeated coronary artery occlusion in pigs under spontaneous breathing were studied. Prazosin, alpha 1-receptor blocker, did not have any effect on the early ischemic dysrhythmia. Yohimbine, which selectively blocks alpha 2-receptor, significantly increased the number of premature ventricular complexes (19 +/- 3----32 +/- 2 PVC; P less than 0.01), but produced no effects on the percentage of appearance of ventricular fibrillation (VF) and ventricular tachycardia (VT). However, nonselective alpha-receptor blocker phentolamine significantly reduced the number of premature ventricular complexes (30.5 +/- 4.5----11 +/- 3 PVC; P less than 0.05), but did not affect the frequency of occurrence of VF and VT. The above results show that alpha-adrenergic mechanisms do not play any important role in the genesis of arrhythmias during ischemia in the pig model.

Adrenergic alpha-Antagonists↗

Effects of right stellate ganglion stimulation on regional myocardial blood flow and ischemic injury in dogs.

The effects of right stellate ganglion stimulation (RSGS) on regional myocardial blood flow (RMBF) and epicardial ST-segment elevation were investigated in the normal and ischemic myocardium of anesthetized dogs. In the non-ischemic areas and despite the augmentation of cardiac work resulting from the increase in heart rate and in myocardial contractile force, RSGS induced no significant changes in RMBF or in the endo/epi ratio. However, after suppression by atenolol of its chronotropic and inotropic effects, RSGS significantly increased the calculated coronary resistance and reduced RMBF, and combined atenolol + phenoxybenzamine treatments abolished these effects. In the ischemic areas, RSGS had no effect on RMBF, endo/epi and I/NI ratios but increased ST-segment elevation, an effect abolished by atenolol. We conclude that (1) during RSGS, alpha-adrenoreceptor-mediated coronary vasoconstriction contributes to oppose beta 1-myocardial stimulation effects on RMBF and endo/epi ratio, (2) further elevation of ST-segment by RSGS is due to enhancement of oxygen requirements by beta 1-adrenoreceptor stimulation.

Animals↗

Increase in oxytocin and vasopressin concentration in the blood outflowing from sella turcica region after superior cervical ganglion stimulation in rat.

The aim of the study was to investigate whether the stimulation of the superior cervical ganglion influences the oxytocin and vasopressin release into the blood in condition of the of the sella turcica integrity. The experiments were performed on male rats under urethane-chloralose anaesthesia. Four 0.7 ml samples of the blood from the sella turcica region flowing through a tube inserted in the maxillary interna vein were collected in the 30, 35, 60 and 90 min of the experiments. The animals were divided into three groups: 1) control, 2) after the exposition of superior cervical ganglion. 3) after the collection of the 1-st sample of the blood the superior cervical ganglion was electrically stimulated for 30 min with trains of pulses. Vasopressin (AVP) and oxytocin (OXY) were determined in the blood plasma by radioimmunoassay. Stimulation of the superior cervical ganglion evoked an significant increase of AVP and OXY release into the blood. The increase of AVP release occurred after 30 min longer latency than the increase of OXY release.

Animals↗

Stellate ganglion stimulation with alpha and beta adrenergic blockade: effect on lung lipids and compliance in cats.

Stellate ganglion stimulation (SGS) can alter lung lipids and reduce static lung compliance, although the mechanisms remain unclear. Phentolamine and propranolol were administered to anesthetized cats prior to stimulation in order to investigate SGS effects on lung lipids and compliance mediated via alpha and beta adrenergic pathways. Analysis of lung lavage revealed that SGS alone decreased cholesterol and the cholesterol/DSPC ratio which might be expected to decrease lung compliance. Alpha and beta blockade alone resulted in no changes from control in cholesterol or DSPC. Alpha blockade plus SGS yielded increased rather than decreased cholesterol and DSPC, while beta blockade prevented any change. A reduction in both static and dynamic lung compliance caused by SGS also was blocked by both alpha and beta blockade. Thus both the alpha and beta blockade prevented the SGS-induced decreases in cholesterol, cholesterol/DSPC ratio, and lung compliance. Furthermore, alpha blockade plus SGS resulted in increased TPL as well as cholesterol and DSPC. The data are consistent with the view that DSPC and cholesterol are released into the subphase by beta adrenergic mechanisms, and that their relative amounts may influence surface properties.

Adrenergic alpha-Antagonists↗

Sphenopalatine ganglion stimulation increases regional cerebral blood flow independent of glucose utilization in the cat.

Regional cerebral blood flow was determined using the tracer [14C]iodoantipyrine and regional brain dissection, and regional cerebral glucose utilization determined using the 2-deoxyglucose method, in the alpha-chloralose-anesthetized cat to evaluate the effect of electrical stimulation of the sphenopalatine (pterygopalatine) ganglion. Unilateral stimulation for either a short period (7-10 min) or a longer period (45 min) resulted in increases in blood flow in the ipsilateral cerebral cortex of up to 45% (parietal cortex) with, in addition, increased flow in the white matter of the corpus callosum (42%). The flow changes for both brief and prolonged stimulation were not significantly different. Flow was not altered in either the brainstem or basal ganglia (caudate nucleus). In contrast to these changes in cerebral blood flow no changes in cerebral glucose utilization were seen in any of the brain areas studied and in particular there were no changes in the areas in which blood flow increased. These data provide clear evidence that the innervation of the cerebral vasculature from the main parasympathetic ganglion can alter cerebral blood flow independent of cerebral metabolism.

Animals↗

Stereochemical analogs of a muscarinic, ganglionic stimulant. 3. 2,3-Substituted bicyclo(2.2.1)hept-5-enes and -heptanes related to 4-(N-(3-chlorophenyl)carbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343).

Preparation of analogs of 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butynyltrimethylammonium chloride (1, McN-A-343), the isomeric 2-trimethylammoniomethyl-3-[N-(4-chlorophenyl)carbamoyloxymethyl]bicyclo [2.2.1]hept-5-ene iodides (10-13), and the corresponding -bicyclo[2.2.1]heptane iodides (14-17) are reported. None of the compounds demonstrated ganglion-stimulating activity similar to 1 or antagonized the effects of 1.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Effect of ganglionic stimulating and blocking agents on the fast components of colonic myoelectrical activity in the rat.

The presence of two types of fast myoelectrical activities, medium fast activity and fast activity, has been demonstrated previously in the electromyogram of colon in normal children and in the rat by the authors. An absence of medium fast activity in Hirschsprung's disease and in experimental aganglionosis of colon in the rat has also been described. In the present study the fast components of colonic myoelectrical activity were analysed during the procedures affecting ganglionic transmission. It was observed that ganglionic stimulants, such as balloon inflation, and intra-arterial injections of acetylcholine and small amounts of nicotine, increased the spike activity and the frequency of medium fast activity without affecting fast activity. The intra-arterial injections of ganglionic blocking agents, such as nicotine in large amounts and pentolinium tartrate, completely abolished the medium fast activity. These observations suggest that the ganglionic activity is responsible for the genesis of medium fast activity and that the absence of cholinergic ganglionic transmission is the most important single factor for the reported altered electromyogram pattern in aganglionosis.

Acetylcholine↗

Increased BBB permeability by parasympathetic sphenopalatine ganglion stimulation in dogs.

The blood-brain barrier (BBB) is a major obstacle for movement of large molecules to and from the brain. Stimulation of the sphenopalatine ganglion (SPG), the major source of parasympathetic innervation to brain vasculature, is known to vasodilate brain vessels, and has recently been shown to also increase the permeability of the BBB in the rat. In this work, we studied the effect of SPG stimulation on BBB permeability in larger animals--Beagle dogs. Left SPG was exposed by lateral approach in five Beagle dogs, and stimulated at 10 Hz. FITC labeled 10 kDa dextran was continuously infused to the left atrium during stimulation, and cerebral angiography was periodically obtained via the vertebral artery. Three control dogs received labeled dextran, without SPG exposure or stimulation. Brains were perfused with saline thoroughly at the end of stimulation, and samples from various regions were taken for fluorescence reading of tissue homogenates. Cerebral vasodilatation was evidenced in all but one dog, whose fluorescence results were consequently excluded from analysis, assuming that its SPG had been damaged by surgery. Fluorescence was significantly higher in the four stimulated compared to the three non-stimulated animals; e.g. mean FITC-dextran concentration in the anterior brain regions was 0.98+/-0.12 ug (mean+/-S.D.) FITC/g brain for experimental animals, and 0.40+/-0.02 for controls (p<0.01). No effect was seen in the pons and cerebellum (0.68+/-0.22 vs. 0.60+/-0.03, NS) whose vascular innervation is supplied by the otic rather than the SPG ganglion. SPG stimulation appears to be an effective way to increase BBB permeability, allowing introduction of large molecules to the brain. This could be a therapeutic method for a wide variety of brain disorders, including tumors and neurodegenerative diseases.

Animals↗

Cerebral blood flow velocities and trigeminal ganglion stimulation. A transcranial Doppler study.

Transcranial Doppler sonography (TCD) patterns of middle cerebral arteries (MCA) were recorded in 10 patients before and during unilateral trigeminal ganglion stimulation (TGS). During TGS, TCD flow velocity significantly decreases in all patients: on both sides in 2 patients, only ipsilaterally to the TGS in 7 patients, and only on the opposite side in the remaining patient. In 2 patients, a controlled progressive hypercapnia test was performed before and during TGS. An enhanced vascular response to increased CO2 concentrations was observed during TGS.

Blood Flow Velocity↗

Effects of trigeminal ganglion stimulation on unit activity of ventral cochlear nucleus neurons.

The trigeminal ganglion sends a projection to the granule and magnocellular regions of the ventral cochlear nucleus (VCN; [J Comp Neurol 419 (2000) 271]), as well as to the cochlea ([Neuroscience 79 (1997) 605; Neuroscience 84 (1998a) 559]). We investigated the effects of electrically stimulating the trigeminal ganglion on unit responses in the guinea-pig VCN. Responses consisted of one, two or more phases of excitation, sometimes followed by a longer inhibitory phase. The latencies to the first excitation peak ranged between 5 and 17 ms from the onset of stimulation. These responses were preceded by a slow wave potential evoked by the stimulation. Applying kainic acid, which eliminates VIIIth nerve responses, diminished the firing rates of VCN units to trigeminal stimulation, and increased their first spike latencies. Cochlear destruction had a similar effect. The responses in VCN evoked by trigeminal ganglion stimulation therefore appear to result from direct stimulation of the trigeminal ganglion-cochlear nucleus pathway, as well as modulation by the trigeminal ganglion-cochlear pathway. Alternatively, a reduction in spontaneous rate of VCN neurons by removal of VIIIth nerve input could explain the decreased response to trigeminal stimulation after cochlear manipulations. The modulation of firing rate in second order auditory neurons by first order somatosensory neurons could influence central auditory targets and may be involved in generating or modulating perceptions of phantom sounds which can be modified by manipulations of somatic regions of the head and neck ("somatic tinnitus").

Action Potentials↗

Increase in vasopressin release into the hypophysial portal blood after superior cervical ganglion stimulation in rat.

The aim of the study was to investigate whether the stimulation of the superior cervical ganglion may influence vasopressin and oxytocin release into the hypophysial portal blood. In urethane-chloralose anaesthesia the pituitary gland was exposed by transpharyngeal approach in rats. The hypophysial portal vessels were transsected in the narrowing between glandular portion of the hypophysis and the infundibulum. The 15 min blood samples from the cut portal vessels were collected before and during electrical stimulation of the superior cervical ganglion. Vasopressin and oxytocin content in the plasma, were determined by radioimmunoassay. In the control samples the vasopressin content amounted to 3.2 +/- 1.03 ng/mL and oxytocin 0.75 +/- 0.3 ng/mL. Stimulation of the superior cervical ganglion evoked an increase (9.6-fold) in vasopressin concentration but not in oxytocin in the blood plasma of hypophysial portal vessels. On the basis of the results obtained, it may be presumed that the sympathetic efferents arising from the superior cervical ganglion induced only vasopressin but not in oxytocin release into the hypophysial portal blood.

Animals↗

Effects of stellate ganglion stimulation on bilateral cochlear blood flow.

The effect of intraneural electrical stimulation of the stellate ganglion (SG) on bilateral cochlear blood flow (CBF) was investigated with laser-Doppler flowmetry. The SG of 15 anesthetized guinea pigs was exposed by a novel surgical approach and stimulated with a specially designed intraneural bipolar platinum-iridium electrode. Bilateral CBF was continuously monitored. Stimulation of 0.25 mA caused a detectable increase of the systemic blood pressure (BP) and a bilateral decrease of the cochlear vascular conductance (R, defined as the ratio CBF/BP). A stimulus of 0.5 mA elicited a statistically significant ipsilateral CBF (CBFi) decrease of 3.6% +/- 5.1% from the baseline and a contralateral CBF (CBFc) decrease of 3.1% +/- 5.5%. That no statistical difference was found between CBFi and CBFc indicates that a unilateral sympathetic stimulation of the SG can cause equal bilateral responses. These responses were accompanied by a significantly increased BP (8.7% +/- 5.2% of baseline) and consequently a greatly decreased R (12.2% +/- 6.5%) of the ipsilateral cochlea. Bilateral sections of the cervical sympathetic trunk below the level of the superior cervical ganglion did not alter the evoked changes in CBF, BP, and R. It is concluded that SG stimulation can decrease the conductivity of the cochlear vessels or the supplying vessels of the cochlea. Additionally, the SG nerve fibers that cause these effects do not pass through the superior cervical ganglion.

Animals↗