Hypogastric Nerve Stimulation Research Articles

Arylazido aminopropionyl atp (ANAPP3) antagonism of cat urinary bladder contractions.

ANAPP3 produces a transient contraction of the urinary bladder of the cat similar to that produced by ATP and hypogastric nerve stimulation. 2 ANAPP3 partially antagonizes the inhibition of pelvic nerve-evoked bladder contractions induced by adenosine, possibly by blocking P1 receptors. 3 ANAPP3 antagonizes contractions of the cat urinary bladder induced by ATP, beta, gamma-methylene ATP, pelvic nerve stimulation and hypogastric nerve stimulation. 4 ANAPP3 produces no antagonism of either noradrenaline-induced inhibition of pelvic nerve-evoked bladder contractions or acetylcholine-induced bladder contractions, thereby substantiating the specificity of the effect of ANAPP3 against purines.

Hormone regulation of adrenaline and noradrenaline release in the inferior mesenteric ganglion of the dog

Studies were carried out on perfused sympathetic ganglia to determine the actions of hormones on their states and functions. The effects of hormones, hydrocortisone, cortin, prostaglandin E 2 (PGE 2), insulin, and triiodothyronine, on the release of adrenaline (A) and noradrenaline (NA) into the superfusate of the inferior mesenteric ganglion (IMG) of the dog were studied in rest and during 3 stimulations: (1) electrical stimulation of lumbar splanchnic and (2) hypogastric nerves; and (3) after acetylcholine application. Hydrocortisone and PGE 2 do not affect A and NA release during all stimulations. Cortin increases the process during (2) and (3). Insulin increases the release of A, though not affecting NA during stimulations 1–3. Triiodothyronine increases the release of NA and decreases that of A during all 3 influences. The mechanism of hormonal action on catecholamine (CA) release by the ganglion's adrenergic structures is discussed, and the presence of insulin receptors in them is suggested.

Non-cholinergic excitatory transmission in inferior mesenteric ganglia of the guinea-pig: possible mediation by substance P.

1. Repetitive stimulation of guinea-pig hypogastric nerves elicited, in addition to the fast cholinergic excitatory potential, a slow depolarization lasting for seconds to minutes in neurones of the isolated inferior mesenteric ganglion. 2. The slow depolarization which could be elicited at a frequency as low as 1-2 Hz for several seconds was not blocked by cholinergic antagonists, but was eliminated in a low Ca2+ solution; it was termed henceforth the non-cholinergic excitatory potential. 3. When the membrane potential was manually clamped, the non-cholinergic potential was associated with three types of membrane resistance change: an increase, a delayed increase and a biphasic change consisting of an initial decrease followed by an increase. 4. In the majority of neurones, conditioning hyperpolarization augmented the non-cholinergic depolarization; in a few neurones, moderate hyperpolarization depressed the latter, whereas stronger hyperpolarization unmasked a low depolarization. 5. The non-cholinergic response was markedly attenuated in the presence of exogenously applied substance P; it was partially suppressed by luteinizing hormone-releasing hormone. 6. Non-cholinergic depolarization could be elicited in the same neurone by stimulation of all four nerve trunks associated with the ganglion. 7. It is suggested that substance P, a peptide, may be the transmitter responsible for the generation of the non-cholinergic potential and that it may be released from collateral endings of primary sensory neurones, thus providing a functional connexion between sensory and autonomic neurones.

Spinal neurones with long projections activated from the abdominal viscera of the cat.

1. Recordings have been made from seventy-three neurones responding to electrical stimulation of pelvic, hypogastric or lumbar colonic nerves, in decerebrate or anaesthetized cats. Fifty-two of the units had long projections that ascended to the first cervical segment, and no units with visceral inputs were found to belong to the spino-cervical tract. Twenty-one units had long descending projections.2. Twenty percent (i.e. 11/46) responded to parasympathetic (pelvic) nerve stimulation (group 1) whilst 80% (35/46) responded to stimulation of hypogastric and/or lumbar colonic nerves (group 2). Ninety percent of group 2 neurones also responded to pelvic nerve stimulation.3. The electrical thresholds for activation of the units indicated that the largest peripheral nerve fibres responsible for the response were of the Adelta size.4. Thirty-one of the neurones had visceral mechanosensitive receptive fields; twenty-one had simple receptive fields in the bladder (seven) or in the colon (fourteen), ten units had compound receptive fields. The response of units with simple receptive fields to mechanical stimulation were either inhibitory or excitatory, and slowly adapting or rapidly adapting. Forty-two units appeared to have no visceral mechano-sensitive receptive fields in spite of showing responses to visceral nerve stimulation.5. Fifty percent of the units tested responded to innocuous somatic stimuli, mostly derived from muscle or joint receptors. Some of the units were found to respond to injections of bradykinin (10-15 mug) into a hindlimb artery.6. Group 1 had predominantly inhibitory visceral receptive fields, and somatic receptive fields in structures innervated from sacral segments of the spinal cord. Group 2 units all received inputs from visceral nerves entering the spinal cord over lumbar segments; many also received projections from sacral segmental inputs. These inputs showed an equal mixture of excitatory and inhibitory visceral receptive fields and convergence from somatic inputs arising from lumbar as well as sacral dermatomes. It seems likely that this group represents units originating in lumbar as well as sacral segments of the cord.7. The possible role of these neurones as mediators of visceral sensations and visceral reflexes is discussed.

Nervous control of the internal anal sphincter of the cat.

1. The effects of sympathetic and parasympathetic efferent nerve stimulation on the activity of longitudinal and circular coats of th anal sphincteric area have been studied on acute animals using extracellular electrical recordings. In addition, the effect of intramural sympathetic nerves stimulation has been investigated on anal sphincteric circular muscle, with the sucrose gap technique. 2. Hypogastric nerve stimulation elicited in anal sphincteric circular muscle slow time course depolarization responses (latency 200-400 msec) which were abolished by alpha-adrenergic blockers (dihydroergotamine, phentolamine). 3. Stimulation of the parasympathetic outflow to the internal anal sphincter (second ventral sacral root: VS2) inhibited spontaneous electrical activity of the circular muscle. Pharmacological arguments lead to the conclusion that the inhibition induced by VS2 stimulation is mediated through intramural non-adrenergic non-cholinergic (purinergic) inhibitory neurones. 4. Rectal distension caused an inhibition of the anal sphincteric circular muscle activity which persisted in the presence of atropine, phentolamine and propranolol, indicating that this inhibition was produced by non-adrenergic non-cholinergic intramural neurones. 5. VS2 stimulation produced only an activation of the longitudinal muscle of the sphincteric area, which was abolished by hexamethonium and atropine; in contrast, hypogastric nerve stimulation gave rise to an inhibition which was blocked by propranolol. These results indicate that the longitudinal muscle receives (1) an excitatory innervation from preganglionic parasympathetic nerves connected with intramural cholinergic neurones, and (2) an inhibitory sympathetic innervation from noradrenergic axons running in the hypogastric nerves. No inhibitory no-adrenergic non-cholinergic innervation was observed in the longitudinal muscle in response to VS2 stimulation. 6. The results obtained from simultaneous stimulation of VS2 and hypogastric nerves indicate that in the anal sphincteric circular muscle the release of noradrenaline from sympathetic nerves is modulated by cholinergic receptors located on noradrenergic nerve endings, muscarinic receptors which can abolish the release of noradrenaline, and probably nicotinic receptors which increase the noradrenaline release. The eventual functional significance of the nicotinic receptors is discussed.

Pharmacological Study on Sympathetic Inhibition of the Urinary Bladder in Dogs

The sympathetic inhibitory mechanism in dog urinary bladder was studied. The bladder contractions induced by electrical stimulation of the pelvic nerve both proximal and distal to the pelvic plexus and by intraarterial administration of tetra-methylammonium (TMA) were inhibited by stimulation of the hypogastric nerve and intraarterial injection of catecholamines. The inhibition by hypogastric nerve stimulation was more potent at the low frequency of pelvic nerve stimulation than at the high frequency. The inhibition of contraction induced by stimulation of the pre-plexal pelvic nerve was antagonized by phentolamine and propranolol, whereas the inhibition of contraction induced by stimulation of the post-plexal pelvic nerve and by TMA treatment were antagonized only by propranolol. It is concluded that inhibition by hypogastric nerve stimulation of bladder contraction induced by pelvic nerve stimulation is composed of two different components. One occurs at the ganglia in the pelvic plexus and is mediated by α-adrenoceptors. The other occurs at the post-plexal pelvic pathway, probably at the ganglia in the bladder wall or on the muscle cells, and is mediated by β-adrenoceptors. Moreover, the α-adrenergic action facilitated the pelvic nerve excitation in its pathway from the ganglionic cell bodies to the muscle cells.

Pharmacological study on sympathetic inhibition of the urinary bladder in dogs.

The sympathetic inhibitory mechanism in dog urinary bladder studied. The bladder contractions induced by electrical stimulation of the pelvic nerve both proximal and distal to the pelvic plexus and by intraarterial administration of tetramethylammonium (TMA) were inhibited by stimulation of the hypogastric nerve and intraarterial injection of catecholamines. The inhibition by hypogastric nerve stimulation was more potent at the low frequency of pelvic nerve stimulation than at the high frequency. The inhibition of contraction induced by stimulation of the pre-plexal pelvic nerve was antagonized by phentolamine and propranolol, whereas the inhibition of contraction induced by stimulation of the post-plexal pelvic nerve and by TMA treatment were antagonized only by propranolol. It is concluded that inhibition by hypogastric nerve stimulation of bladder contraction induced by pelvic nerve stimulation is composed of two different components. One occurs at the ganglia in the pelvic plexus and is mediated by alpha-adrenoceptors. The other occurs at the post-plexal pelvic pathway, probably at the ganglia in the bladder wall or on the muscle cells, and is mediated by beta-adrenoceptors. Moreover, the alpha-adrenergic action facilitated the pelvic nerve excitation in its pathway from the ganglionic cell bodies to the muscle cells.

モルモット輸精管におけるGuanethidineの交感神経遮断作用に対するPhenoxybenzamineの影響

The interaction of guanethidine (Guan) and phenoxybenzamine (PBA) has been studied for the responses to hypogastric nerve stimulation (HS) and transmural stimulation (TS) of guinea pig vas deferens. Response to TS (40 pulses at 20 Hz) was fully inhibited and the peak of response to HS at 20 Hz was inhibited by about 60% by the addition of Guan (3×10-5M). After treatment with PBA (1×10-8-1×10-7M), the peak of response to HS was significantly inhibited and sometimes completely by the addition of Guan. But when the concentration of PBA was increased to 1×10-6M or 1×10-5M, the reduction of the peak of response to HS by Guan became less concentration-dependent. Inhibitory effect of Guan on response to TS was also prevented by pretreatment with PBA (1×10-6-1×10-5M). On the other hand, after treatment with PBA (1×10-7M or 1×10-6M) methamphetamine (1×10-5M) fully restored the response to TS but scarcely restored the peak of response to HS in the presence of Guan. After the addition of methamphetamine, inhibitory effect of Guan on the peak response to HS was prevented soon and completely by washout of Guan. PBA seems to cause inhibition of Guan uptake at nerve endings. But after treatment with PBA the conduction of impulse to nerve endings seems to be partially blocked by the addition of Guan and methamphetamine does not seem to antagonized the conduction blocking activity induced by Guan.

Ketamine Acts on the Peripheral Sympathetic Nervous System of Guinea Pigs

The effects of ketamine on the peripheral sympathetic nervous system were studied in vitro by observing the amplitude of the nerve-mediated contraction of the vasa deferentia isolated from guinea pigs. Ketamine dissolved in the perfusate of an organ bath was applied to the tissues for 30 minutes and then washed out with a perfusate lacking ketamine for 90 minutes. Ketamine in concentrations of 10(-8) and 10(-7) g/ml had no effect on contraction induced by hypogastric nerve (preganglionic) stimulation. At 10(-6) g/ml, the drug had no significant effect during application but was associated with increased contractions during washout. At 10(-5) and 10(-4) g/ml, the drug showed a dose-related depression during application and an increase in contractions during washout after a 10(-5) g/ml. Ketamine, 10(-5) g/ml, increased contraction following transmural (postganglionic) stimulation and had a depressant effect at a concentration of 10(-4) g/ml. It is concluded (1) that ketamine has dual effects on the nerve-mediated contraction of the vasa defentia and (2) that cardiovascular responses to ketamine include peripheral effects of ketamine on sympathetic ganglia.

Changes in penile volume during some cardiovascular reflexes and reactions in rabbit

The effect of various cardiovascular reflexes and reactions on the plethysmographically recorded penile volume in rabbit was investigated. Stimulation of the aortic nerve or direct stimulation of the carotid sinus produced increase in penile volume, while carotid occlusion produced decrease. Brief volume load or protoveratrine given into the right atrium produced increase in penile volume. Asphyxia, hypercapnia, hypoxia, cyanide and lobeline produced decrease in penile volume, while hypocapnia increased it. Moderate blood taps decreased penile volume, while hypocapnia increased it. Moderate blood taps decreased penile volume. With the exception of the response to asphyxia all these reactions required intact vasomotor nerves. Clonidine increased penile volume if vasomotor nerves were intact but decreased it if the penis was decentralized. Penile volume decreased in shivering animals but increased on warming. Carotid occlusion impaired erectile responses to hypogastric and pelvic nerve stimulation. In certain experiments this effect was more pronounced in the latter case. It is concluded that the medullary neuron pool responsible for penile vasomotor tone participates in general reflex cardiovascular homeostasis and that this may have implications for normal erectile responses.

Aminoglycoside antibiotics and sympathetic ganglionic transmission.

The effects of streptomycin, gentamicin, tobramycin and amikacin on transmission in sympathetic ganglia have been studied using the guinea pig isolated hypogastric nerve-vas deferens preparation. These aminoglycoside antibiotics produce dose-related sympathetic blockade at concentrations greater than the common therapeutically effective antibiotic concentrations.

The role of the hypogastric nerve in bladder and urethral activity of the dog.

1. Stimulation of the hypogastric nerves increased the pressure in both the bladder and urethra of anaesthetized female dogs. 2. The responses were reduced but not abolished by the alpha-adrenoceptor antagonist phentolamine, whereas the beta-adrenoceptor antagonist propranolol was either without effect or increased the responses. Atropine, methysergide and hexamethonium were without effect. 3. Close arterial injection of phenylephrine increased and isoprenaline decreased urethral pressure but both produced only a slight increase in bladder pressure. 4. Hypogastric nerve stimulation reduced subsequent responses of the bladder and urethra to pelvic nerve stimulation or to close arterial injection of acetylcholine. Isoprenaline, but not phenylephrine, also had an inhibitory action and 5-hydroxytryptamine enhanced the responses. 5. In the presence of hexamethonium the inhibitory action of isoprenaline still occurred but 5-hydroxytryptamine no longer enhanced the responses, suggesting that 5-hydroxytryptamine acts on the ganglia and isoprenaline acts, at least partially, on smooth muscle. 6. These results suggest that the role of the hypogastric nerves may be to modify inputs to the bladder and urethra as well as to act directly on the smooth muscle.

Actions of substance P on sympathetic neurons

When applied to the neurons of isolated inferior mesenteric ganglia of guinea pig, substance P consistently caused a membrane depolarization accompanied, in many instances, by intense neuronal discharges. The substance P-induced depolarization or spikings were not abolished by d-tubocurarine and/or atropine or by superfusing the ganglia with a low Ca/high Mg solution. Repetitive stimulation of hypogastric nerves elicited a slow non-chol inergic depolarization which exhibited electrophysiological and pharmacological properties similar to those of substance P-induced depolarization. When ganglion cells were desensitized by continuous application of substance P, preganglionic stimulation failed to induce the slow non-cholinergic depolarization. These results suggest the possibility that the slow non-cholinergic depolarization may be due to the synaptic release of substance P.

EFFECTS OF SURUGATOXIN ON ADRENERGIC ALLYINNERVATED TISSUES

Effects of surugatoxin (SGTX), a new ganglionic blocking agent on adrenergically innervated tissues: guinea pig isolated atria and vas deferens were investigated. SGTX (1, 10 /JM) markedly reduced the cardiostimulatory response of the atria to nicotine and also partially the response to l,l-dimethyl-4-phenylpiper- azinium (DMPP) and 5-hydroxytryptamine, without affecting responses to noradrenaline, tyramine and histamine. The contractile response of the vas deferens to nicotine, DMPP and hypogastric nerve stimulation was markedly reduced by SGTX (1, 10 /;M), whereas that to noradrenaline, acetylcholine and transmural stimulation was not affected. These results indicate that SGTX has an antagonistic action on nicotinic receptors in these tissues as well as in sympathetic ganglia and' in guinea pig ileum.

Some effects of imipramine on micturition and their relevance to its anti-enuretic activity

Voiding was induced in conscious cats by an infusion of saline into the bladder via a chronically implanted catheter. Imipramine (1 mg/kg), a dose equivalent to 25 mg for a 7 year old child, increased the functional bladder capacity by maxima of between 35 and 160%. an effect lasting some 15hr. The effect was not due to the local anaesthetic, muscle depressant or cholinolytic activities of imipramine. Imipramine potentiated detrusor relaxation evoked by hypogastric nerve stimulation in anaesthetized cats, an effect explained by inhibition of noradrenaline reuptake. Since the role of the hypogastric innervation in micturition is as yet incompletely understood, it is not possible to state whether the anti-enuretic activity of imipramine can be attributed to this action or whether an effect at the central level is more important.

The urethral pressure response to hypogastric and pudendal nerve stimulation (author's transl)

The urethral pressure response to hypogastric and pudendal nerve stimulation (author's transl)

Characteristics of the internal anal sphincter and the rectum of the vervet monkey.

1. The physiology of the internal anal sphincter of the vervet monkey was investigated. 2. Strips of sphincter in vitro contracted to noradrenaline and adrenaline; adrenoceptors were mainly alpha-excitatory. Strips of rectal circular muscle relaxed to noradrenaline and contained both inhibitory alpha- and beta-adrenoceptors. 3. All strips contracted to acetylcholine. After hyoscine or atropine, high doses of acetylcholine relaxed all strips by stimulating intramural inhibitory neurones as relaxations were blocked by tetrodotoxin and hexamethonium. Nicotine and DMPP gave relaxations with similar characteristics. 4. It was concluded that relaxations to acetylcholine, nicotine and DMPP were not adrenergic as relaxations still occurred in strips from sympathetically denervated or reserpinized animals. The block of these relaxations by propranolol and guanethidine was considered to be unrelated to their actions as adrenergic blocking drugs. 5. All strips relaxed to field electrical stimulation (1--5 Hz) through stimulation of intramural inhibitory neurones as tetrodotoxin blocked these relaxations. Adrenergic blocking drugs, prior reserpinization or prior section of the hypogastric nerves did not block these responses. The relaxations were not therefore adrenergic. 6. 5-Hydroxytryptamine relaxed all strips but was not the transmitter in relaxations to acetylcholine, DMPP or nicotine, nor to field electrical stimulation, as desensitization of strips of 5-HT did not alter these responses. 7. The circular smooth muscle of the internal anal sphincter had a dense terminal adrenergic innervation which rapidly decreased orad. 8. In vivo, hypogastric nerve stimulation relaxed the rectum but contracted the sphincter. Sacral nerve root stimulation caused an after-contraction in both rectum and sphincter. In vivo, a close arterial injection of adrenaline or noradrenaline inhibited the spontaneous contraction waves of the rectum, but contracted the sphincter. Both these responses were blocked by phentolamine. 9. It was concluded that the internal anal sphincter is a discrete high pressure zone which was excitatory cholinergic and adrenergic innervations and an inhibitory non-adrenergic innervation.

Diethyldithiocarbamateによる射精の抑制効果ならびに副性腺内モノアミンの変動について

Effects of diethyldithiocarbamate(DDC) on erection and ejaculation were investigated and monoamine levels in central nervous system, gonad and accessory glands were determined in dogs. Intraperitoneal administration of 50, 75 and 100 mg/kg of DDC suppressed ejaculation 1 hour after administration, although penial erection did occur. This suppression of ejaculation was recovered to some extent 3 hours after DDC and completely recovered 24 hours after DDC. One hour after the administration of 100 mg/kg of DDC, noradrenaline (NA) level in the caudate and serotonin (5-HT) level in the posterior hypothalamus decreased significantly, as compared with the control. However, there were no significant changes in the regions of anterior hypothalamus and hippocampus which are known to play an important role in sexual behavior. In the epididymis, NA and adrenaline levels decreased significantly, though 5-HT levels increased, as compared with those of the control. In the prostate and posterior urethra, NA levels decreased significantly, as compared with the control. The seminal emission induced by hypogastric nerve stimulation induced a gradual rise in the posterior urethral pressure. When the pressure reached the maximum level, rhythmic alterations of the pressure considered to be a phenomenon associated with ejaculation occurred. DDC (100 mg/kg) abolished both seminal emission and rhythmic alterations of the posterior urethral pressure. These findings indicate that the sperm transport may be inhibited by decrease of NA level in accessory glands.

Mianserin — An analysis of its peripheral autonomic actions

The autonomic profile of mianserin has been compared with that of yohimbine, phentolamine, phenoxybenzamine and desmethylimipramine. The effects of mianserin on tyramine and noradrenaline pressor responses in the pithed rat were consistent with α-adrenoceptor antagonist and uptake blocking properties. In isolated tissue experiments, the selectivity of mianserin for pre- and postsynaptic α-adrenoceptors was similar to that of phentolamine. In pithed rats mianserin antagonised the pressor response produced by clonidine and reversed the inhibitory actions of clonidine on cardiac nerve stimulation. In contrast mianserin only caused slight reversal of the inhibitory effects of clonidine on hypogastric nerve stimulation. Uptake blockade itself inhibits hypogastric nerve stimulation and this could counteract any antagonism of the effects of clonidine at the presynaptic α-adrenoceptor. The results demonstrate the uptake blocking properties of mianserin and its antagonism at both pre- and postsynaptic α-adrenoceptors.

Slowly-developing depolarization of neurones in the guinea-pig inferior mesenteric ganglion following repetitive stimulation of the preganglionic nerves

Intracellular recordings were made from cells of the isolated guinea-pig inferior mesenteric ganglion. Stimulation of both hypogastric nerves at 30 Hz for 2 sec caused a slowly developing depolarization (SD) and fall in cell input resistance which reached a peak 10–30 sec after the end of stimulation. The amplitude of the SD was increased in a graded manner if the stimulus voltage was increased. The SD was unaffected by tubocurarine, atropine or guanethidine, but was blocked by removing external Ca. These results suggested that the SD was caused by the release of some substance from a large number of nerve terminals.