PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Ganglionic Stimulants”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed2005

Non-invasive in vivo infrared laser spectroscopy to analyse endogenous oxy-haemoglobin, deoxy-haemoglobin, and blood volume in the rat CNS.

Oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb) are chromophores present in biological tissues. Near infrared spectroscopy (NIRS) is a non-invasive methodology based on the low extinction coefficient of tissue in the near infrared region. NIRS can be used to measure changes in the concentration of these chromophores, i.e., haemoglobin, in muscular tissue. In the present work, NIRS has been used for the non-invasive monitoring of HbO2, Hb, and blood volume (V: representing total haemoglobin, i.e., HbO2+Hb) in vivo in the whole rat brain. This has been performed by means of prototype instrumentation based on optic fibre probes placed in contact with the head of anaesthetised rats held in a stereotaxic frame. A preliminary test of the instrument has been performed on human muscle, i.e., lateral gastrocnemius, in order to evaluate the ability of the instrument to detect oxygenation changes. Afterwards, the effects of pharmacological treatments, such as systemic amphetamine and nicotine treatments on the CNS have been detected.

Amphetamine↗
PubMed2005

The role of CGRP and nicotinic receptors in centrally evoked facial blood flow changes.

The release of CGRP in humans is associated with the occurrence of migraine headaches. The vasoactive neuropeptide is released by afferent neurones originating in the peripherally located trigeminal ganglion supplying the dura mater. The role of CGRP in migraine is further supported by recently released data showing that the CGRP-antagonist BIBN4096BS is clinically effective for the treatment of migraine headaches. Yet, the trigger for CGRP release during migraine attacks is not identified. It is suggested that the peripheral CGRP release during a migraine attack might be either triggered by direct activation of afferent dural neurones, or, by indirect activation via the central nervous system. Recently, we were able to show that the CGRP-antagonist BIBN4096BS is able to inhibit vasodilation induced by trigeminal ganglion stimulation. Now, we extend our studies to the investigation of facial blood flow changes induced by electrical stimulation of the brainstem trigeminal nucleus caudalis (TNC). Here, we show that stimulation of the TNC leads to a pronounced increase of facial blood flow. The nicotinic antagonist Hexamethonium reduced the evoked flow by approximately 50% (30 mg/kg), while the muscarinic antagonist Atropin did not influence the stimulation evoked blood flow. Application of BIBN4096BS (0.3 mg/kg, i.v.) diminished the evoked flow almost completely. Therefore, we conclude that CGRP represents the key player in TNC-induced facial vasodilation, while activation of nicotinic receptors modulates centrally induced peripheral neurogenic vasodilation.

Animals↗
PubMed2005

A neuroactive steroid, allotetrahydrocorticosterone inhibits sensory nerves activation in guinea-pig airways.

We examined the effects of a neuroactive steroid, allotetrahydrocorticosterone on the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). Allotetrahydrocorticosterone (0.0001-1.0 microg/ml) dose-dependently inhibited electrical field stimulation-induced guinea-pig bronchial smooth muscle contraction, but not the substance P-induced contraction at 1.0 microg/ml. Allotetrahydrocorticosterone (0.01-1.0 microg/ml) also reduced the capsaicin-induced release of substance P-like immunoreactivity from guinea-pig airway tissues in a dose-dependent manner. The inhibitory effect of allotetrahydrocorticosterone on electrical field stimulation-induced bronchial contraction were reduced by the pretreatment of voltage-dependent K+ channel blockers, tetraethylammonium (1 mM). This evidence suggests that allotetrahydrocorticosterone negatively modulate the activation of C-fibers and substance P release from their endings in airway tissues via the opening of voltage-dependent K+ channels.

Animals↗
PubMed2005

Molecular characterization of pheromone biosynthesis activating neuropeptide from the diamondback moth, Plutella xylostella (L.).

Pheromone biosynthesis activating neuropeptide (PBAN) produced in the subesophageal ganglion stimulates pheromone production in the pheromone gland. A cDNA isolated from female adult heads of the diamondback moth (Plutella xylostella (L.)) encodes 193 amino acids including PBAN, designated as Plx-PBAN, and four other neuropeptides (NPs): diapause hormone (DH) homologue, alpha-NP, beta-NP and gamma-NP. All of the peptides are amidated in their C-termini and shared a conserved motif, FXPR(or K)L structure, as reported from other PBAN cDNAs. Plx-PBAN consists of 30 amino acids, the shortest PBAN so far reported. Plx-PBAN exhibited below 50% homology, compared with other known PBANs. The Plx-DH homologue is structurally different from DH of Bombyx mori. The length of Plx-beta-NP (16 amino acids) was the shortest and showed relatively low similarity, whereas gamma-NP (10 amino acids in length) was the longest among examined gamma-NPs. When female adults were injected with synthetic Plx-PBAN, pheromone production showed a maximal increase 1h post-injection. RT-PCR screening revealed that Plx-PBAN cDNA was expressed in all examined body parts, with the highest expression level in the head of female adults. Analysis of RT-PCR products indicated the Plx-PBAN sequence was identical in all examined body parts of both sexes. Phylogenetic analysis revealed that the Plx-PBAN gene is distantly related to other PBANs, demonstrated by the relatively low similarity.

Amino Acid Sequence↗
PubMed1997

Spectral analysis of electrograms during ventricular tachycardia in a canine model: relation with epicardial isochronal maps.

The purpose of this study was to assess the capability of magnitude-squared coherence and bicoherence to differentiate monomorphic ventricular tachycardia (MVT) and polymorphic ventricular tachycardia (PVT) in a canine model and to relate these results to the epicardial isochronal maps on a beat-to-beat basis. Unipolar electrograms were simultaneously recorded from the surface of both ventricles with a 127-lead sock electrode array in 12 open-chest anesthetized dogs. The sampling frequency was 500 Hz. Atrioventricular block was induced by formaldehyde injection into the atrioventricular node. The left anterior descending coronary artery was occluded for 60 minutes under ventricular pacing (140 beats/min). During reperfusion, 12 MVT episodes lasting more than 42 seconds were recorded. Left stellate ganglion stimulation induced five PVT episodes lasting more than 42 seconds. Each of these recordings was divided into seven segments of 3,072 points (6.144 seconds). After visual selection, 104 segments were extracted and classified as 73 MVT and 31 PVT segments. Magnitude-squared coherence was estimated as the cross-spectrum from two epicardial signals (on the right and left ventricles, respectively), normalized with the respective autopower spectrum. Bicoherence was estimated as the bispectrum normalized with the autopower spectrum. Magnitude-squared coherence correctly identified 96% of MVT and 81% of PVT segments for a total accuracy of 91%. Bicoherence estimated with the left ventricular lead correctly identified 100% of MVT and 77% of PVT segments with an accuracy of 93%. Beat-to-beat epicardial maps of MVT displayed a cluster of sites of origin close to the reperfusion area, while the sites of origin from beats during PVT were much more dispersed over both ventricles. A strong and significant correlation was found between the number of electrodes with the earliest epicardial activation and coherence (r = .76, P < .0001) and bicoherence (r = .68, P < .0001), respectively. A high and significant correlation was also found between both spectral estimators (r = .74, P < .0001). Coherence and bicoherence discriminated accurately between MVT and PVT. Coherence achieved better results compared with bicoherence. Coherence and bicoherence measurements showed a quantitative relation with the spatial dispersion of the sites of origin. Both spectral techniques seemed powerful enough to be used in the development of implantable devices.

Animals↗
PubMed1999

Effects of PNU-109,291, a selective 5-HT1D receptor agonist, on electrically induced dural plasma extravasation and capsaicin-evoked c-fos immunoreactivity within trigeminal nucleus caudalis.

We studied the effects of PNU-109291 [(S)-(-)-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-isoc hroman-6-carboxamide], a receptor agonist showing 5000-fold selectivity for primate 5-HT1D versus 5-HT1B receptors (Ennis et al., J. Med. Chem. 41, 2180-2183), on dural neurogenic inflammation and on c-fos like immunoreactivity within trigeminal nucleus caudalis evoked by electrical and chemical activation of trigeminal afferents, respectively. Subcutaneous injection of PNU-109291 in male guinea pigs dose-dependently reduced dural extravasation of [125I]-labeled bovine serum albumin evoked by trigeminal ganglion stimulation with an IC50 of 4.2 nmol kg(-1). A dose of 73.3 nmol kg(-1) blocked the response completely. The selective 5-HT1B/1D receptor antagonist GR-127935 (> or = 2 micromol kg(-1) i.v.) prevented this effect. In addition, the number of c-fos immunoreactive cells within guinea pig trigeminal nucleus caudalis induced by chemical meningeal stimulation (intracisternally administered capsaicin) was reduced by more than 50% with PNU-109291 (> or = 122.2 nmol kg(-1) administered s.c. 45 min before and 15 min after capsaicin). These data indicate that the 5-HT1D receptor subtype plays a significant role in suppressing meningeal neurogenic inflammation and attenuating trigeminal nociception in these guinea pig models. Since 5-HT1D receptor mRNA and protein are expressed in trigeminal ganglia but not vascular smooth muscle, the 5-HT1D receptor subtype may become a useful therapeutic target for migraine and related headaches.

Animals↗
PubMed1986

Efficacy of diltiazem in two experimental feline models of sudden cardiac death.

The potential role of calcium entry blockers in the prevention of life-threatening arrhythmias associated with acute myocardial ischemia and reperfusion is still controversial. In 98 anesthetized cats, the effect of diltiazem was examined in two experimental models. In protocol I, ventricular tachycardia or fibrillation was consistently induced by the interaction between a 2 minute coronary artery occlusion and a 30 second left stellate ganglion stimulation. After three trials under control conditions, if the same pattern of arrhythmia was induced, the drug under study was administered and three additional trials were performed. In 16 animals the administration of saline solution did not modify the pattern of arrhythmias. In contrast, diltiazem (0.1 mg/kg body weight plus 0.2 mg/kg per h) abolished both ventricular tachycardia and fibrillation that had occurred in 64 and 36%, respectively, of the cats in the control state. In protocol II, a 20 minute coronary artery occlusion was released in three groups; one served as the control group, one received diltiazem 15 minutes before occlusion and one received diltiazem 3 minutes before reperfusion. The incidence of reperfusion ventricular fibrillation was 62% (16 of 26) in the control group. It was significantly (p less than 0.05) reduced by diltiazem administered before the occlusion to 25% (4 of 16), whereas it was not affected when diltiazem was administered just before reperfusion (7 [47%] of 15). These results indicate that diltiazem exerts a striking protective effect against the malignant arrhythmias induced by the combination of acute myocardial ischemia and sympathetic hyperactivity. Diltiazem was also effective in reducing the incidence of life-threatening reperfusion arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation.

CNI-1493 is a potent anti-inflammatory agent, which deactivates macrophages and inhibits the synthesis of proinflammatory mediators. The objective of the present study was to identify the role of the central nervous system (CNS) and efferent vagus nerve signaling in CNI-1493-mediated modulation of acute inflammation in the periphery. CNI-1493 was administered either intracerebroventricularly (i.c.v., 0.1-1,000 ng/kg) or intravenously (i.v., 5 mg/kg) in anesthetized rats subjected to a standard model of acute inflammation (subcutaneous (s.c.) injection of carrageenan). I.c.v. CNI-1493 significantly suppressed carrageenan-induced paw edema, even in doses at least 6-logs lower than those required for a systemic effect. Bilateral cervical vagotomy or atropine blockade (1 mg/kg/h) abrogated the anti-inflammatory effects of CNI-1493 (1 microg/kg, i.c.v. or 5 mg/kg, i.v.), indicating that the intact vagus nerve is required for CNI-1493 activity. Recording of the efferent vagus nerve activity revealed an increase in discharge rate starting at 3-4 min after CNI-1493 administration (5 mg/kg, i.v.) and lasting for 10-14 min (control activity=87+/-5.4 impulses/s versus CNI-1493-induced activity= 229+/-6.7 impulses/s). Modulation of efferent vagus nerve activity by electrical stimulation (5 V, 2 ms, 1 Hz) of the transected peripheral vagus nerve for 20 min (10 min before carrageenan administration and 10 min after) also prevented the development of acute inflammation. Local administration of the vagus nerve neurotransmitter, acetylcholine (4 microg/kg, s.c.), or cholinergic agonists into the site of carrageenan-injection also inhibited acute inflammation. These results now identify a previously unrecognized role of efferent vagus nerve activity in mediating the central action of an anti-inflammatory agent.

Acetylcholine↗
PubMed2002

Electrophysiological effects of tachykinin agonists on sympathetic ganglia of spontaneously hypertensive rats.

This study investigated the cellular basis for the enhanced ganglionic responsiveness to NK1 agonists in the spontaneously hypertensive rat (SHR) in comparison to their normotensive counterpart, the Wistar-Kyoto (WKY) rat. Rats for in vivo studies were anesthetized with pentobarbital and treated with chlorisondamine (10.5 micromol/kg). Extracellular recordings from the external carotid nerve showed a greater responsiveness of decentralized SHR superior cervical ganglia (SCG) to intravenous injection of SP (32 nmol/kg). Blood pressure and heart rate were increased in SHRs, whereas WKY rats responded with a decrease in blood pressure and only slight tachycardia. Membrane properties of SCG neurons, as shown by intracellular microelectrode recordings, were similar between strains. Picospritzer application of the NK1 agonist GR-73632 (100 microM, 1 s) evoked slow depolarization and increased neuron excitability. Spontaneous firing was evoked only in some neurons. Depolarization amplitudes were similar between strains; however, the NK1 agonist depolarized a greater number of neurons in hypertensive rats. In conclusion, SHRs are more responsive to ganglion stimulation by NK1 agonists due to a greater number of responsive cells within the SCG rather than an enhanced responsiveness of individual neurons.

Analysis of Variance↗
PubMed1996

3-Aryl-1,2-diacetamidopropane derivatives as novel and potent NK-1 receptor antagonists.

Early structure-activity studies on racemic tryptophan ester and amide NK-1 antagonists 5-7 led to the discovery that the potency of the series could be markedly increased by moving the carbonyl function in these molecules to an off-chain position as in the 3-aryl-1,2-diacetamidopropane 9. Further medicinal chemistry incorporating this change resulted in the discovery of a novel series of highly potent aryl amino acid derived NK-1 antagonists of the R stereoisomeric series (IC50's = 100 pM to > 5 microM). Compounds in this series were shown to be competitive antagonists using an in vitro NK-1 smooth muscle assay, and this data correlated well with observed human NK-1 binding affinities. Two of these agents, (R)-25 and (R)-32, blocked intrathecal NK-1 agonist-driven [Ac-[Arg6,Sar9,Met(O2)11]- substance P 6-11 (Ac-Sar9)] nociceptive behavior in mice. Both compounds potently blocked the neurogenic dural inflammation following trigeminal ganglion stimulation in the guinea pig after intravenous administration. Further, upon oral administration in this model, (R)-32 was observed to be very potent (ID50 = 91 ng/kg) and have a long duration of action (> 8 h at 1 micrograms/kg). Compound (R)-32, designated LY303870, is currently under clinical development as an NK-1 antagonist with a long duration of action.

Amides↗
PubMed2002

Captopril treatment reverses erectile dysfunction in male stroke prone spontaneously hypertensive rats.

The involvement of antihypertensive therapy in the pathology of hypertension associated male erectile dysfunction is unclear. Stroke prone spontaneously hypertensive rats (SHRSP) were treated chronically with the angiotensin converting enzyme (ACE) inhibitor captopril or placebo, normotensive rats served as controls. Mean arterial and intracavernosal pressure were measured during the induction of erection by autonomic ganglion stimulation. SHRSP-placebo treated rats were hypertensive and had a blunted erectile response. Captopril treatment returned both the blood pressure and erectile response to control levels. Therefore, ACE inhibitor therapy may not be responsible for the erectile dysfunction observed in treated hypertensive subjects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Neurogenic model of migraine.

Activation of peripheral trigeminal fibers induces neurogenic inflammation in rat dura mater, as well as vascular and mat cell changes. These changes parallel an increase of vasodilating and permeability promoting peptides in venous effluent of the cephalic circulation. The experimental model of electrical trigeminal ganglion stimulation or systemic capsaicin administration has proven effective in detecting cellular activation in brainstem trigeminal nuclei. Animal experimental models of trigeminovascular activation and the effects of antimigraine drugs on functional and morphological consequences of such activation provide the background for further models and for developing pharmacological strategies in this field.

Animals↗
PubMed1997

Evidence for nicotinic receptors potentially modulating nociceptive transmission at the level of the primary sensory neuron: studies with F11 cells.

F11 cells are a dorsal root ganglion (DRG) cell line used to model the function of authentic type C, peptidergic, nociceptive neurons. The cellular events underlying the antinociceptive effects of (+/-)-epibatidine, a nicotinic acetylcholine receptor (nAChR) ligand that is 200-fold more potent than morphine, is unknown. The present study investigated the ability of cholinergic channel activators (ChCAs) to effect nAChR-gated ion flux and modulate the release of substance P (SP), a neuropeptide identified to play a critical role in nociception. The prototypical agonists (-)-nicotine and (-)-cytisine, the ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium, the novel ChCA ABT-418 [(S)-3-methyl-5-(-1-methyl-2-pyrrolidinyl)isoxazole], and (+/-)-epibatidine evoked a concentration-dependent stimulation of rubidium (86Rb+) efflux with EC50 values of 14.2 +/- 1.6, 63.4 +/- 24, 3.8 +/- 2.0, 29.8 +/- 2.6, and 0.019 +/- 0.001 microM as well as maximal intrinsic activities of 100, 97, 69, 75, and 102%, respectively. The noncompetitive nAChR antagonist mecamylamine potently antagonized (-)-nicotine-evoked ion flux, whereas the competitive antagonist dihydro-beta-erythroidine was a weak antagonist, giving support to an alpha3beta4 nAChR subtype. In addition, concentrations of (+/-)-epibatidine, similar to those necessary to induce maximal 86Rb+ efflux, evoked spontaneous release of SP from these cells, which was blocked by mecamylamine. Furthermore, prolonged exposure to (+/-)-epibatidine desensitized the functional response of the nAChR in this cell line (IC50 = 12 +/- 9 nM). These findings in F11 cells provide a model to investigate the role nAChRs play in modulating DRG cell function, and may lead to insights into the role these receptors have in modulating nociceptive transmission.

Analgesics, Non-Narcotic↗
PubMed1994

Influence of acetonylgeraniin, a hydrolyzable tannin from Euphoria longana, on orthostatic hypotension in a rat model.

Acetonylgeraniin, an active principle isolated from the seeds of Euphoria longana Lam. (Sapindaceae), reversed the fall in arterial blood pressure in conscious hypertensive rats (SHRs) with orthostatic hypotension induced by injection of hexamethonium into animals subjected to 90 degrees head-up tilts for 60 seconds. However, acetonylgeraniin failed to affect prazosin-induced orthostatic hypotension. Plasma noradrenaline (NA) and mean blood pressure were elevated dose-dependently by an intravenous injection of acetonyl-geraniin into the rats; this increase in blood pressure was totally abolished by prazosin. Failure of hexamethonium or pentolinium, the blockers of ganglionic nicotinic receptors, to influence the NA releasing action of acetonylgeraniin ruled out the participation of ganglionic stimulation. This NA-releasing action of acetonylgeraniin was, however, totally abolished by the inhibitors of noradrenergic nerve terminals, guanethidine or bretylium. Also, the activity of this tannin was not modified by adrenalectomy. Thus, a direct release of NA from the noradrenergic nerve terminals by acetonylgeraniin seems responsible for the reversing of orthostatic hypotension.

Animals↗
PubMed1983

Nerve growth factor: stimulation of polymorphonuclear leukocyte chemotaxis in vitro.

Topical application of mouse nerve growth factor (NGF) to superficial skin wounds of mice has previously been shown to accelerate the rate of wound contraction. Results of the present study reveal that NGF in the presence of plasma is also chemotactic for human polymorphonuclear leukocytes in vitro, and the concentration of NGF required for this effect is similar to that which stimulates ganglionic neurite outgrowth. This property does not arise from liberation of the C5a fragment of complement, nor does it require the known enzymic activity of NGF. (NGF inactivated with diisopropyl fluorophosphate is equally active.) We conclude that NGF can display biological effects on cells of nonneural origin and function, and this feature might play a role in the early inflammatory response to injury.

Animals↗
PubMed1980

Protective effect of verapamil on vulnerability to ventricular fibrillation during myocardial ischaemia and reperfusion.

The effects of verapamil on vulnerability to ventricular fibrillation were studied in 55 chloralose-anaesthetised dogs. Ventricular fibrillation threshold was measured before and during a 10 min period of left anterior descending coronary artery occlusion and following abrupt release of occlusion. The action of intravenous verapamil (0.01 mg.kg-1.min-1, following a 0.1 mg.kg-1 bolus) on vulnerability to fibrillation was examined before and during coronary artery occlusion and reperfusion. While the infusion of verapamil did not alter the ventricular fibrillation threshold in the nonischaemic myocardium, the vulnerable period threshold was raised and the incidence of spontaneous ventricular fibrillation was reduced both after coronary artery occlusion and release. Since cardiocardiac sympathetic reflexes are elicited in response to coronary artery occlusion, the effect of verapamil on vulnerability during left stellate ganglion stimulation and during noradrenaline infusion was investigated. Verapamil completely prevented the reduction in vulnerable period threshold during sympathetic nerve stimulation or noradrenaline infusion. This study suggests that the antifibrillatory action of verapamil during coronary artery occlusion may be, in part, related to antagonism of enhanced adrenergic input to the heart, while the mechanism of protection during reperfusion is as yet uncertain.

Adrenergic Fibers↗
PubMedDate not supplied

Effects of dopamine, N-N-di-n-propyl dopamine, and (R)- and (S)-sulpiride on guinea pig blood pressure.

Effects of intravenous injections of dopamine (DA) and N-N-di-n-propyl dopamine (DPDA) on mean arterial pressure (MAP) and heart rate (HR) were studied in urethane-anesthetized guinea pigs. DA and DPDA produced dose-related reductions in MAP. DA produced a biphasic change in HR, an initial decrease followed by an increase, while DPDA produced only a decrease in HR. Phentolamine and hexamethonium did not affect the depressor effects of DA, but virtually abolished the depressor effects of DPDA. Thus, DA appears to lower MAP primarily by direct vasodilation; whereas DPDA acts predominantly by inhibiting the sympathetic nervous system. Hexamethonium prevented the bradycardia induced by DA and DPDA, but had no effect on the DA-induced tachycardia. (R)- and (S)-sulpiride produced hypotensive effects of short duration that were due to their weak alpha-adrenergic blocking activity. In addition, the (R) enantiomer produced a secondary pressor effect that was abolished by phentolamine and hexamethonium. (R)-sulpiride potentiated pressor effects of the ganglionic stimulant 1-1-dimethyl-4-phenylpiperazinium iodide (DMPP), suggesting that it facilitated sympathetic nerve activity. This study demonstrates that guinea pig blood pressure can be used to differentiate between the neuronal and vascular origins of hypotension produced by DA agonists. The use of (R)- and (S)-sulpiride for further localizing the actions of DA and DPDA is complicated by their alpha-adrenergic blocking activity and by an apparent facilitatory effect of (R)-sulpiride on sympathetic nerve transmission.

Animals↗