Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Ganglionic Blockers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,171 records · Page 65Linked to original sources
PubMed1995

Lack of vascular hyporesponsiveness to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis.

BACKGROUND/AIMS: In cirrhosis, the mechanism(s) for vascular hyporesponsiveness to vasoconstrictors such as, alpha 1-adrenoceptor agonists, vasopressin and angiotensin II, are unclear. Moreover, vascular reactivity to substances such as L-type calcium channel activators is unknown. METHODS: Thus, pressor dose-response curves to vasoconstrictors [phenylephrine (an alpha 1-agonist, 0.1-500 micrograms/kg) angiotensin II (10-500 ng/kg), vasopressin (0.01-5 IU/kg), and Bay K 8644 (an L-type calcium channel activator, 0.5-50 micrograms/kg)] were obtained in normal rats and in rats with secondary biliary cirrhosis. All experiments were performed in ganglionic-blocked animals to limit the influence of cardiovascular reflexes. Doses of vasoconstrictor necessary to obtain a 40 mmHg increase in arterial pressure (D40) were calculated. RESULTS: Compared to normal animals, rats with cirrhosis had significantly higher D40 values for angiotensin II (171 +/- 57 vs. 344 +/- 41 ng/kg), phenylephrine (2.6 +/- 0.2 vs. 26.4 +/- 10.7 micrograms/kg) and vasopressin (73 +/- 19 vs. 401 +/- 150 mU/kg). Pressor responses to Bay K 8644 did not differ between normal rats and rats with cirrhosis (8.8 +/- 0.9 vs. 10.5 +/- 2.1 micrograms/kg). CONCLUSIONS: In conclusion, this study shows that cirrhosis produces vascular hyporeactivity to phenylephrine, vasopressin and angiotensin II but not to Bay K 8644. Therefore, cirrhosis impairs certain constrictor mechanisms which are shared by phenylephrine, angiotensin II and vasopressin but which do not contribute to the vascular response to Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

Release of VIP-like immunoreactivity in response to dopamine agonists, insulin hypoglycemia and feeding in conscious dogs.

VIP levels were measured by radioimmunoassay in peripheral venous blood of conscious dogs. Bolus injections of the dopamine agonists apomorphine, 0.05 mg/kg, and bromocriptine, 0.2 mg/kg, were found to increase VIP levels from approximately 5 pmol/l to 150 pmol/l. The release responses were abolished by pretreatment with dopamine antagonists (haloperidol 0.1 mg/kg or halopemid 0.1 mg/kg) and by hexamethonium (1 mg/kg) a blocker of ganglionic transmission. Vagotomy did not inhibit the dopamine agonist induced output of VIP. Vagal activation by means of feeding or insulin hypoglycemia caused only minor rises of VIP levels (5-10 pmol/l). It is concluded that dopamine agonists stimulate the release of VIP from populations of neurons other than those affected by vagal and sympathetic activation. Possible sites of action for the VIP releasing effect exerted by dopamine agonists are discussed. Furthermore, it is suggested that some of the peripheral effects exerted by dopaminergic drugs are exerted via a previous release of VIP.

Animals↗
PubMedDate not supplied

Oxytocin modulation of intrathoracic sympathetic ganglionic neurons regulating the canine heart.

Substance P and vasoactive intestinal peptide are known to activate intrathoracic sympathetic neurons which regulate the heart. In the present series of experiments, when 1 I.U. of oxytocin in 0.1 cc of normal saline was administered into the cranial poles of stellate or the middle of middle cervical ganglia cardiac rate and force were augmented. The locations of ganglionic loci which, when injected, resulted in cardiac changes varied between animals. Twenty active sites were identified in the 12 dogs investigated. When the vehicle (0.1 cc of normal saline) was injected into these active sites minimal cardiac responses were induced in one instance. When 1 or 2 I.U. of oxytocin was administered into the superior vena cave of seven animals slight systemic hypotension occurred in two of these animals. Cardiac responses were induced when oxytocin was reinjected into active intrathoracic ganglionic sites after whole body administration of hexamethonium (10 mg/kg IV), but not after local administration of timolol into the ganglia. Thus, it appears that oxytocin can activate intrathoracic ganglionic neurons involved in efferent sympathetic cardiac regulation. That such responses persist in the presence of nicotinic blockade, but not following beta-adrenergic blockade of ganglionic neurons, indicates that oxytocin modifies beta-adrenergic and not nicotinic receptors on neurons in these ganglia.

Animals↗
PubMed1995

Pressor and tachycardic responses to intravenous substance P in anesthetized rats.

Intravenous injection of 3-33 nmol/kg of substance P (SP) caused pressor and tachycardic responses in anesthetized rats. The responses were not blocked by a ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine blocked both responses. beta-Adrenoceptor blockade attenuated only the tachycardic response, and alpha-adrenoceptor blockade attenuated only the pressor response. These findings indicated that the effects of SP to increase blood pressure and heart rate are due to sympathetic ganglion stimulation. Studies with adrenalectomized rats showed that stimulation of the adrenals by SP contributes to both responses but makes a greater contribution to the tachycardic response. These observations raise the possibility that the tachykinin innervation of sympathetic ganglia and the adrenal medulla may be involved in the local regulation of blood pressure and heart rate.

Adrenal Glands↗
PubMed1996

Cholecystokinin depolarizes neurons of cat pancreatic ganglion.

The effect of cholecystokinin octapeptide (CCK-8) on membrane potential and conductance of cat pancreatic ganglion neurons was studied in vitro by means of intracellular microelectrode recording methods. Microejection of S-CCK-8 and NS-CCK-8 evoked, by direct action, a slow, reversible membrane depolarization. The majority of neurons tested were more sensitive to S-CCK-8. The depolarizing response to S-CCK-8 and NS-CCK-8 was accompanied in different neurons by a variable change in membrane permeability to Na+ and/or K+. The effects of S-CCK-8 and NS-CCK-8 were mediated by the CCKB receptor. The results suggest that S-CCK-8 and NS-CCK-8 increase the excitability of pancreatic ganglion neurons by acting on postsynaptic CCKB receptors.

Animals↗
PubMed1983

Efficacy and toxicity of drug combinations in treatment of physostigmine toxicosis.

Atropine, in combination with 1 of 6 other drugs, was tested in mice for the ability to prevent death by an otherwise lethal dose of the cholinesterase inhibitor, physostigmine. The atropine dose (4 mg/kg, i.p.) was kept constant, while the dose of the other drug in the pair was tested in 5 geometrically spaced doses, ranging down to 1/16 of the maximum dose (which caused no gross behavioral signs). Atropine alone saved 20% of the mice. The combination of atropine and benactyzine saved 100% of the mice at all 5 doses of benactyzine; similar complete protection was afforded by the combination of atropine and the largest dose of an oxime, TMB4 (15 mg/kg). Over 80% survivals were achieved with the larger doses of atropine combinations involving hexamethonium, mecamylamine, and diazepam. No enhanced protection occurred with atropine combinations with the oxime, 2-PAM. The toxicity of the effective combinations, when used in high doses without physostigmine challenge, revealed that deaths occurred over a narrow range of doses of all combinations except atropine/diazepam. An additive toxic effect of atropine was suggested with its combinations with TMB4, mecamylamine, and diazepam, whereas no additive toxicity occurred with combinations involving hexamethonium or benactyzine (i.e., the LD50 of the combinations was about the same as for hexamethonium or benzactyzine alone). The combinations with the best therapeutic safety ratio were with diazepam (no deaths at a dose 10 times that which saved 100% of mice) and benactyzine (no deaths at a more than 50-fold dose).

Animals↗
PubMed1991

Vasopressin increases blood glucose in pygmy goats (Capra hircus) by an alpha-adrenergic mechanism.

1. Twelve adult pygmy goats were used to investigate the mechanism of vasopressin (VP) induced hyperglycaemia. 2. VP (0.4 microgram/kg or 0.75 microgram/kg body weight) injected i.p. produced a long lasting hyperglycaemia. 3. This hyperglycaemia was partly reversed by alpha-adrenergic antagonists with an affinity to alpha 1- and alpha 2-adrenergic receptors (phentolamine) or to alpha 2-adrenergic receptors (yohimbine). An alpha 1-adrenergic agonist (xylometazoline) produced a short-term hyperglycaemia. 4. The ganglion blocking agent hexamethonium also reversed VP's hyperglycaemic effect. 5. It is concluded that VP's hyperglycaemic effect in pygmy goats is due to an increase in sympathetic outflow and not to a direct action on the liver.

Adrenergic alpha-Agonists↗
PubMed1990

High-frequency stimulation of the facial nerve results in local cortical release of vasoactive intestinal polypeptide in the anesthetised cat.

Local cortical release of vasoactive intestinal polypeptide (VIP) was measured using a sensitive radioimmunoassay following direct electrical stimulation of the facial nerve in the anaesthetised cat. During activation of the facial nerve dilator pathway VIP was released at the cortex and collected into a physiological superfusate, its concentration increasing from 4.2 +/- 1.2 to 15.5 +/- 2.4 pmol/l. Administration of the nicotinic ganglion blocking agent hexamethonium (10 mg/kg i.v.) eliminated this response demonstrating that the release is mediated via an autonomic ganglion. Given previous experiments that have demonstrated that stimulation of the facial nerve leads to a neurogenically mediated dilatation of the cerebral vasculature, these data further implicate VIP as the transmitter in this pathway.

Animals↗
PubMed1991

Intracellular recording of spontaneous activity of canine intracardiac ganglion cells.

Intracellular recordings were made from 302 canine intracardiac ganglion cells with intact synaptic connections. Fifty-two % of these cells exhibited spontaneous membrane potential changes consisting primarily of miniature excitatory postsynaptic potential (EPSP)-like depolarizations upon which an action potential or burst of action potentials was sometimes evoked. Most of the spontaneous potential changes are presumed to be synaptically mediated involving nicotinic mechanisms because they were blocked by low Ca2+/high Mg2+ and hexamethonium solutions.

Action Potentials↗
PubMed1995

Intrathecal injection of an oxytocin-receptor antagonist attenuated postnephrectomy natriuresis in the male rat.

We have previously shown that oxytocin (OT) is a major humoral mediator in postnephrectomy natriuresis. As immunoassayable OT has been demonstrated in the spinal cord, the aim of this investigation was to determine whether OT receptors in the spinal cord are also involved in this natriuresis. The experiments were performed on anesthetized male rats. Before acute unilateral nephrectomy, an oxytocin-receptor antagonist was injected intrathecally in the thoracolumbar region in rats. Postnephrectomy natriuresis was attenuated by this injection but not by intrathecal injection of artificial cerebrospinal fluid. Our results suggest that OT receptors within the spinal cord may influence the autonomic nervous regulation of renal function. In an additional experiment, intravenously infused hexamethonium did not prevent the adaptive natriuresis in the remaining kidney. We conclude that OT receptors in the spinal cord are involved in the postnephrectomy natriuresis, possibly as a component in the afferent signal pathway.

Animals↗
PubMed1995

The use of topical 4% lidocaine in spheno-palatine ganglion blocks for the treatment of chronic muscle pain syndromes: a randomized, controlled trial.

To assess the efficacy of 4% topical lidocaine in spheno-palatine blocks, a randomized controlled trial was carried out on patients with chronic muscle pain syndromes. Sixty-one patients (42 with fibromyalgia (FM) and 19 with myofascial pain syndrome (MPS)) completed the trial. Outcome measures included pain intensity, a daily pain diary, headache frequency, sensitivity to pressure using a dolorimeter, anxiety, depression, and sleep quality. Patients were randomized to receive either 4% lidocaine or sterile water (placebo) 6 times over a 3-week period. Both subjects and investigators were blind to treatment allocation. The results showed that 4% lidocaine had no superiority over placebo in any of the outcome measures. Twenty-one subjects (35%) showed a decrease in pain which was greater than 30% of their baseline value. Of these 21 subjects, 10 received lidocaine and 11 received placebo. These data suggest that, in this population, 4% lidocaine is no better than placebo in the treatment of chronic muscle pain.

Administration, Topical↗
PubMed1976

5-Hydroxytryptamine and narcotic-analgesics interactions in the intestine.

The effects of 5-hydroxytriptamine (5-HT), 5-HT blocking agents, morphine, narcotic-antagonists and ganglionic blocking agents were tested in the dog intestine by close intra-arterial injection. Morphine, as 5-HT, induced an immediate increase in the intestinal tonus followed by phasic contractions. When 5-HT was injected immediately after cessation of morphine induced phasic contractions, a significant potentiation of the 5-HT induced intestinal contraction could be observed. The potentiation could be demonstrated for other narcotic-analgesics like dextromoramide and it is specific for 5-HT. 5-HT blocking agents like LSD, BOL, and cyproheptadine did not block either 5-HT or morphine. However, bufotenidine, a neural tryptaminergic blocking agent, blocked the effects of both 5-HT and morphine. The effects of 5-HT and morphine upon intestinal motility were also diminished by ganglionic depolarizing agents such as nicotine and DMPP. This effect could, however, be prevented by the pretreatment with hexamethonium. These results seem to confirm the hypothesis of a 5-HT mediator role in the intestinal contractile effect induced by the narcotic-analgesics. On the other hand, narcotic-antagonists such as nalorphine and cyclazocine, not only lacked the 5-HT potentiation effect but also prevented the 5-HT potentiation induced by morphine. Cyclazocine also showed a long lasting 5-HT blocking effect. These results seem to show that the 5-HT potentiating effect of morphine in vivo is very specific and characteristic of the narcotics and thus could be implicated in some of their central effects.

Analgesics, Opioid↗
PubMed1990

Non-opioid effects of N-methyl levallorphan in the anaesthetised rat.

1. The effects of the quaternary opioid antagonist N-methyl levallorphan upon cardiovascular responses to non-opioid agonists has been studied in the urethane-anaesthetised rat. 2. N-methyl levallorphan showed an initial nicotinic agonist effect followed by pronounced ganglion blocking activity after intravenous administration. These effects are observed at doses only 2-fold higher than those required to block cardiovascular responses to [Met] enkephalin. 3. The narrow selectivity of N-methyl levallorphan makes this compound inappropriate for opioid antagonist studies where nicotinic receptors may be involved.

Acetylcholine↗
PubMed1985

Isolation of a polypeptide from the venom of Bungarus multicinctus that binds to ganglia and blocks the ganglionic transmission in mammals.

A 15,000 dalton polypeptide purified from Bungarus multicinctus venom (which normally copurifies with alpha-bungarotoxin) was characterized biochemically and its biological effects were studied. This polypeptide, P15, had an aminoacid composition and molecular weight different from those of both alpha- and beta-bungarotoxin. It inhibited the ganglionic transmission in the guinea-pig hypogastric nerve-vas deferens preparation and did not block, even at very high concentrations, the neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. In the same preparations alpha-bungarotoxin was unable to block the response at the ganglionic synapse while it was fully active in blocking the neuromuscular transmission. However, a pretreatment of the vas deferens preparation with alpha-bungarotoxin prevented the inhibitory effect of P15. 125I-Labeled P15 showed a specific and saturable binding to rat superior cervical ganglia homogenate and to a Torpedo postsynaptic membrane fraction. The binding of P15 to ganglia was inhibited by curare. The binding was Ca2+ dependent. The density of binding sites was of 300 fmol/mg of protein in the ganglion and 500 fmol/mg of protein in Torpedo membranes. The amount of P15-binding sites in ganglia was not modified by denervation, indicating that P15 binds to postsynaptic receptors. The binding of 125I-labeled P15, both in ganglia and Torpedo membranes, was inhibited by alpha-bungarotoxin. P15 had a Ca2+-dependent phospholipase A2 activity. Lowering Ca2+ concentration in incubation media affected the phospholipase A2 activity more than binding properties and inhibition of phospholipase activity with p-bromophenacyl bromide did not affect the activity of P15 on vas deferens preparation, suggesting that the phospholipase activity is not necessary for the activity of P15 on nicotinic receptors. Our results suggest that P15 toxin may be a specific and valuable probe for studying the ganglionic nicotinic receptor.

Animals↗
PubMed1989

Evidence for an involvement of substance P, but not cholecystokinin-like peptides, in hexamethonium-resistant intestinal peristalsis.

It has previously been found that, in the presence of naloxone, the ganglionic blocking drug hexamethonium fails to completely block peristaltic motility in the isolated ileum of the guinea-pig. This hexamethonium-resistant peristaltic activity is coordinated by enteric nerves since it is abolished by tetrodotoxin. In the present study the neurotransmitter circuitry of this type of peristalsis was studied by means of specific antagonists. Atropine totally suppressed hexamethonium-resistant peristalsis. This type of peristalsis was also strongly inhibited by the tachykinin antagonist, spantide, if a concentration sufficient to antagonize neuronally located substance P receptors was employed. In contrast, the cholecystokinin antagonist, lorglumide, caused only a slight inhibition of hexamethonium-resistant peristalsis. Both substance P and the cholecystokinin-related peptide, ceruletide, potently stimulated the hexamethonium-resistant type of peristaltic activity. These data indicate that, after blockade of nicotinic acetylcholine receptors, tachykinins mediate neuroneuronal coordination of peristalsis whereas acetylcholine acting via muscarinic receptors may be primarily responsible for neuromuscular transmission. Cholecystokinin-like peptides appear to play a modulator rather than a mediator role in hexamethonium-resistant peristalsis.

Animals↗