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Recto-anal motility response to bladder distension was studied under general anaesthesia in 12 patients undergoing intestinal resection for Crohn's disease of the small intestine or colonic cancer. The effect of epidural anaesthesia on anal tone and on the motility response to bladder distension was studied in six of these patients. An anal pressure increase on bladder distension was observed in all individuals. No motility response was noted in the rectum. The anal pressure response to bladder distension was abolished by epidural anaesthesia. It was concluded that anal pressure in man under general anaesthesia was tonically influenced by the thoracolumbar sympathetic outflow. An excitatory vesico-anal reflex was demonstrated. It appears as this reflex is mediated via the spinal cord.

1. The effects of electrical stimulation of the peripheral end of the cervical vagal nerve on jejunal motility were investigated in anaesthetized cats, pretreated with guanethidine, with sectioned splanchnic nerves and ligated adrenal vessels. Motility was monitored as volume changes of an intraluminal balloon. 2. Vagal stimulation elicited frequency-dependent hypermotility with a short latency. Relaxatory events were also observed, which could indicate the presence of a non-adrenergic inhibitory pathway. 3. After atropine treatment, contractions and relaxations could still be elicited. The former were compared to cholinergic contractions and showed a lower maximal amplitude and a longer latency to onset. Moreover, they were antagonized by 80-100% by the opioid receptor antagonist, naloxone. 4. Vagal stimulation after hemicholinium, given in order to deplete the preganglionic acetylcholine content, elicited naloxone-sensitive contractions. This suggests that a subpopulation of the vagal preganglionic fibres is non-cholinergic. 5. Isolation of the balloon-containing segment did not qualitatively alter the responses, indicating that the vagal fibres reach the small intestine via the paravascular mesenteric nerves. 6. It is concluded that cholinergic and non-adrenergic, non-cholinergic (NANC) contractions, as well as relaxations, could be elicited by efferent vagal stimulation. The NANC contractions seem to result from the activation of opioid receptors causing disinhibition of a tonic neurogenic restraint on the gut muscle.

The neural pathways and possible transmission mechanisms of the integrated autonomic nervous control of the urinary bladder and anorectum, were investigated in chloralose anaesthetized cats. Bladder distension and spontaneous detrusor contractions increased internal anal sphincter-tone, a response which was blocked by an alpha-adrenoceptor antagonist. Moreover, a nicotinic transmission step was present. Both the afferent and efferent limbs of the reflex were conveyed in the postganglionic hypogastric nerves and the preganglionic lumbar splanchnic nerves. Intact connection with the central nervous system was therefore essential. Contrasting to the specific reflex response in the internal anal sphincter, bladder distension also elicited a nociceptive vaso-pressor response. Rectal motility appeared to be unaffected by bladder distension.

Duodenal or jejunal motility (monitored as pressure changes in a saline-perfused intraluminal catheter) was studied in anaesthetized rats, vagotomized and pretreated with adrenergic blocking agents. In the duodenum (but not the jejunum), atropine or the selective muscarinic M1 and M3 receptor antagonists, pirenzepine and 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP), respectively, augmented the spontaneous contractile activity. This effect could be abolished either by nicotinic ganglionic receptor antagonism with hexamethonium, or with morphine. Moreover, blockade of the synthesis of nitric oxide by N omega-nitro-L-arginine elicited hypermotility both in the duodenum and the jejunum, and also this response was abolished by hexamethonium. It is proposed from the present results that the rat small is controlled by non-adrenergic, non-cholinergic inhibitory as well as excitatory motor neurons. The latter motor neurons seem to be modulated by muscarinic, nitroxergic or opioidergic mechanisms.

The effects of blocking nitric oxide synthase with the arginine analog N omega-nitro-L-arginine (L-NNA) were investigated in anaesthetized cats, vagotomized and pretreated with guanethidine and atropine. Spontaneous NANC jejunal motility (recorded as the volume changes of an intraluminal balloon) was markedly increased in a dose-dependent and stereospecific manner. The effect of L-NNA was partly reversed by L-arginine, the substrate for nitric oxide (NO) synthesis. Thus, this study presents evidence for a tonic inhibitory influence, via the release of NO, on small intestinal motility in vivo. Furthermore, relaxations upon the L-NNA-induced hypermotility could be elicited by vagal nerve stimulation, which may suggest the existence of another NANC inhibitory transmitter. Hexamethonium abolished such relaxations but did not affect the tone or phasic activity after L-NNA.

Some factors known to affect jejunal motility (recorded as volume changes of an intraluminal balloon) were investigated in anaesthetized cats (ether-chloralose) pretreated with guanethidine and atropine. Indomethacin, morphine (both compounds administered systemically) or vagal nerve stimulation elicited jejunal excitatory motor responses. The effect of indomethacin seemed to be independent of cyclooxygenase inhibition and probably did not involve opioid receptors. It is suggested that the spasmogenic stimuli caused jejunal hypermotility by inhibiting tonically active, inhibitory motor neurons that are intrinsic to the gut. Furthermore, when the jenunal tone had been raised by indomethacin or morphine spontaneous relaxations were observed, and these could be mimicked by vagal stimulation. Hexamethonium antagonized these relaxations but did not attenuate the drug-induced jejunal hypermotility.

Experiments were performed in chloralosed cats where gastric motility was recorded by the "volume method". Mucosal and serosal nociceptive stimulations were accomplished by local heating to 45-52 degrees C. Heating generally elicited gastric relaxations, mainly due to activation of extrinsic inhibitory reflexes, but mucosal heating sometimes caused contractile responses which were resistant to nicotinic and adrenergic blockade. The contractions were, however, blocked by atropine and, further, could not be demonstrated after degeneration of splanchnic afferents. On the basis of these and earlier results it is suggested that the gastric contractions induced by mucosal nociceptive stimulation are due to axon reflexes, conveyed by splanchnic afferents that, possibly via release of substance P, make non-nicotinic reflex contacts with intramural excitatory cholinergic neurons.

Experiments were performed in chloralosed cats, laparotomized with ligated adrenals and spinalized in the cervical region. Blood pressure, heart rate and gastric motility were monitored. Stimulations were performed in two brain stem regions, viz. a "control region" including the nucleus ambiguous and a "dorsal region" approximately corresponding to the dorsal vagal nucleus and the solitarius complex. From both regions were regularly elicited gastric motor responses that were either excitatory, biphasic or inhibitory in direction, and always associated with prompt bradycardia and hypotension. After hexamethonium blockade of the "conventional" efferent vagal excitatory and relaxatory fibres to the stomach, stimulation of the control region no longer augmented gastric motility, while gastric contractions which could be abolished by atropine or vagotomy were produced from the dorsal region. The bradycardia and hypotension responses from both regions were also blocked by hexamethonium and then stimulations often led to delayed pressor responses, resistant to both vagotomy and atropine. The present results, together with previous findings (Delbro et al. 1981, 1982) suggest that the hexamethonium-resistant gastric contractions, elicited by stimulation of the mentioned dorsal region of the brain stem, are due to antidromic activation of afferent gastric vagal fibres with excitatory collaterals to intramural cholinergic neurons.

The effects of dopamine on intestinal blood flow (IBF) and intestinal contraction rate (ICR), and on mean arterial pressure (MAP) and heart rate (HR) were studied in eight cats before and during epidural analgesia (EDA). Before EDA, dopamine 5 and 10 micrograms.kg-1.min-1 had no effect on IBF, MAP and HR, but the higher infusion rate decreased ICR by 71 +/- 19% (mean +/- 1 s.e.mean) (P less than 0.01). EDA significantly increased IBF when intestinal arterial pressure was maintained at an unchanged level by means of a pump, and transiently increased ICR and intestinal tone, but reduced MAP by 46 +/- 8% (139 +/- 11 to 75 +/- 9 mmHg, P less than 0.01) and HR by 26 +/- 3% (248 +/- 7 to 184 +/- 8 beats.min-1, P less than 0.01). During EDA, dopamine increased IBF further, the response being similar at both infusion rates. 5 micrograms.kg-1.min-1 increased HR by 26 +/- 7 beats.min-1 (P less than 0.01) and MAP by 19 +/- 9 mmHg (ns). The corresponding values at 10 micrograms.kg-1.min-1 were 65 +/- 14 beats.min-1 (P less than 0.01) and 35 +/- 8 mmHg (P less than 0.01), respectively, Vascular autoregulation appeared to be unaffected by dopamine and EDA. The effect of dopamine on ICR was not significantly different to what was seen before EDA. It is concluded that the effects of dopamine on IBF, MAP and HR were markedly different during EDA as compared to before the block and that ICR was reduced by dopamine, while it was transiently increased by EDA.(ABSTRACT TRUNCATED AT 250 WORDS)

In anesthetized rats treated with guanethidine, the pylorus was ligated. A catheter was inserted into the stomach via the mouth and anchored by a ligature around the cervical oesophagus. The catheter was used for instillation into the stomach of a fixed volume (9 ml) of either isotonic or 1 M NaCl and for the recording of intragastric pressure. Neurogenic modulation of gastric motility caused by either solution was analysed by studying the effect of the systemic administration of the ganglionic blocker hexamethonium on gastric tone and on phasic motor activity. Gastric motility was not significantly changed by hexamethonium in the animals that had been subjected to isotonic NaCl. After intragastric treatment with 1 M NaCl, however, hexamethonium caused increased gastric tone and decreased phasic motor activity. An analysis of these results suggests that 1 M NaCl activated vagal non-adrenergic, non-cholinergic relaxatory and cholinergic excitatory motor neurons, respectively. These chemically induced modulations of gastric motility were dependent on the spinal cord and, most probably, were due to activation of the mucosal sensory endings of the splanchnic nerves, leading to reflex spinovagal motor adjustments.

A method to study electrically induced distal colonic motility in the rat in vivo is reported. The animals were anaesthetized with methohexital and chloralose and were artificially ventilated. Motility of a segment (2 cm) of the distal colon was monitored as volume changes of an intraluminal balloon, introduced via the anus. Local electrical stimulation of the wall of the segment was achieved by means of a bipolar electrode folded around the gut. Stimulations produced reproducible contractile responses in a frequency dependent fashion. Stimulation characteristics resembled those of other autonomic neuro-effector systems. The adrenergic neuron-blocker, guanethidine, significantly lowered colonic tone, but had no other effects on spontaneous or electrically induced motility. Atropine significantly lowered colonic tone. After the administration of this compound the electrically induced contractions were significantly smaller with a shorter duration and, furthermore, appeared upon the cessation of stimulation ('off' or 'rebound' contraction). Following the administration of tetrodotoxin (TTX, given close i.a. via a cannula with its tip in distal aorta) basal colonic tone and the number of spontaneously occurring contractions increased. The amplitude and duration of the electrically induced responses were significantly attenuated and, furthermore, appeared as 'rebound' contractions which were preceded by a relaxation. Such TTX-resistant responses may be myogenic, but a neurogenic origin cannot be excluded. The present study showed that local electrical stimulation of the distal colon elicits cholinergic contractions, but also atropine- and TTX-resistant motor responses.

Gastric motor responses, recorded as volume changes of an intragastric balloon, were induced by the close i.a. administration of bradykinin (0.75-4 micrograms) in chloralose-anaesthetized cats. The animals were vagotomized and the adrenals were ligated at the outset of the experiments. Prior to autonomic blocking agents bradykinin elicited relaxatory or biphasic motor responses. Following nicotinic ganglionic receptor blockade bradykinin caused predominantly gastric contractions. Such excitatory responses were antagonized by 80-100% by atropine, suggesting a dominant neurogenic component. An hypothesis is put forward that the observed gastric contractions result from a bradykinin-induced activation of an axon reflex arrangement confined to thin sensory nerve fibres which, by substance P release from intramural collaterals, excite postganglionic cholinergic motor neurones.

Experiments were performed on chloralosed cats, pretreated with guanethidine and hexamethonium and with ligated adrenals. The motility of an arterially isolated colonic segment was monitored by a volumetric method. Colonic contractions were induced either by electric stimulation of the centrally cut lumbar splanchnic nerves, or by close i.a. injections of acetylcholine (ACh). Close i.a. injections of substance P (SP) were performed in order to test the degree of SP-receptor blockade. Blockade of colonic SP-receptors, either by close i.a. administration of large amounts of SP itself or by Spantide, a competitive SP-receptor antagonist, markedly reduced or abolished the neurally induced colonic contractions, while responses to ACh were unchanged. These results indicate a role for SP, or a closely related peptide, as an intermediate neurotransmitter in the neurally induced colonic responses. Thus, the present study gives support to the hypothesis that non-nicotinic, non-adrenergic colonic contractions, in response to electric stimulation of sympathetic nerves, are due to an antidromic activation of sensory neurons with peripheral excitatory collaterals which release SP, in turn activating the colonic smooth muscle, mainly via a muscarinic mechanism.

Electrical stimulation of the feline vagal or splanchnic nerves after hexamethonium blockade of nicotinic ganglionic transmission produces gastric contractions, suggesting antidromic activation of thin afferents. The present experiments were performed to examine whether substance P is involved as a transmitter in such gastric responses. Cats were anesthetized with chloralose, laparotomized and the adrenals were ligated. The left greater splanchnic nerve, proximal to the celiac ganglion, and the left or right cervical vagal nerve were dissected, cut and placed on electrodes for peripheral stimulation. Gastric motility was monitored with a balloon. Hexamethonium was administered i.v. as well as i.a. to the stomach. Nerve stimulations produced powerful gastric contractions, which were antagonized by large doses (approximately 0.8 mumol) of substance P administered i.a. to the stomach. Similarly, the gastric contractions elicited by vagal or splanchnic nerve stimulations were reduced to at least 60% of control by the specific substance P antagonist (D-Pro2, D-Trp7,9)-SP administered i.a. (0.4-1.3 mumol). The present results support the concept that substance P is associated with gastric excitatory motor responses, possibly elicited by antidromic activation of thin afferent nerve fibres.

Experiments were performed on cats anaesthetized with chloralose and treated with adrenoceptor blocking agents. Distal colonic and rectal motility were selectively recorded by a volumetric method. The effects of muscarinic and ganglionic nicotine receptor blockade on motor responses induced by graded efferent electrical pelvic nerve stimulation (PNS) were studied. Stimulation at low current strength evoked contractions in both the colon and the rectum, which were sensitive to atropine and to hexamethonium. High intensity stimulation elicited distal colonic contractions resistant to both atropine and hexamethonium. Similar excitatory responses to high strength PNS were also observed in the rectum, though not in all experiments. Stimulation at intermediate intensities evoked distal colonic and rectal relaxations which were resistant to atropine but blocked by hexamethonium. The results indicate that PNS influences colonic and rectal motility by activation of at least three discrete non-adrenergic nervous pathways: (1) low-threshold excitatory fibres involving nicotinic and muscarinic transmission, (2) high-threshold excitatory fibres with a non-muscarinic, non-nicotinic transmission mechanism, (3) inhibitory fibres with an intermediate stimulus intensity threshold, exerting their effect by a non-muscarinic mechanism involving a nicotinic step.

Experiments were performed on chloralose-anaesthetized cats, pretreated with guanethidine and with ligated adrenals and sectioned splanchnic nerves. The animals were paralysed and artificially ventilated. Jejunal motility was recorded by an intraluminal balloon, as volume changes at a constant pressure. Cervical or abdominal vagal afferent stimulation was performed before and after the administration of atropine. In both circumstances jejunal contractions were elicited. The latency of onset and the duration of the responses were significantly shorter before than after atropine. Strength-duration and frequency-response relationships, respectively, did not differ significantly prior and subsequent to atropine. Naloxone (0.05-0.5 mg kg-1 i.v.) blocked these reflexly induced atropine-resistant jejunal contractions, as did section of the contralateral vagus. Possible mechanisms of action of these putative opioid receptor-mediated neurogenic effects are discussed. The present study demonstrates that non-adrenergic, non-cholinergic, naloxone-sensitive jejunal contractions can be elicited as a vago-vagal reflex, where the receptive field seems to be located within the abdominal cavity.

Stimulation of the sectioned cervical vagal nerve of anaesthetized cats (ether-chloralose), pretreated with guanethidine and atropine, in the peripheral direction produced gastric relaxation as well as jejunal and ileal contraction. The administration of indomethacin markedly enhanced intestinal tone and the amplitude of spontaneous phasic activity while the basal gastric motility was essentially unchanged. This suggests that endogenous prostaglandins exert an inhibitory influence on intestinal motility. The vagally induced gastric relaxation was significantly inhibited by indomethacin, with could suggest that prostaglandins modulate non-adrenergic, non-cholinergic inhibitory neurotransmission in the stomach.

The possible involvement of purinoceptors in the parasympathetic nervous control of large intestinal motility was investigated in cats anaesthetized with chloralose and treated with adrenolytics. Distal colonic and rectal motor responses to efferent pelvic nerve stimulation (PNS) and drugs injected close i.a., were recorded by a volumetric method. Single dose i.a. injections of alpha, beta-methylene ATP (mATP) induced colonic and rectal contractions which were resistant to atropine, hexamethonium and indomethacin, as well as to the nerve blocking agent tetrodotoxin. Repeated injections of mATP were followed by attenuated motor responses and eventually complete tachyphylaxis to the compound developed. In the presence of atropine, or a combination of hexamethonium and atropine, contractions elicited by PNS were inhibited during mATP tachyphylaxis. In contrast, prior to such anticholinergic drugs, or in the presence of hexamethonium alone, pelvic nerve mediated contractions persisted despite mATP tachyphylaxis, which did not affect the colonic and rectal contractions evoked by acetylcholine or histamine. The results suggest that P2-purinoceptors are involved in non-adrenergic, non-cholinergic large intestinal excitatory motor responses to PNS.

The inhibitory motor effect of the sympathetic gastrointestino-gastrointestinal (GI-GI) reflex was studied in cats with isolated innervated ileal (Thiry-Vella) loops. They were subjected to acute experiments under chloralose-gallamine anaesthesia where gastric volume, arterial blood pressure and heart rate were continuously monitored. The cervical vagi were sectioned and used for efferent stimulation. The hypothalamus was systematically explored by means of stereotaxically guided electrodes. When the abdomen was undisturbed, gastric contractile responses to central stimulation were virtually absent, regardless of whether a vagally induced tone was present or not. Distension of the isolated intestinal loop induced marked inhibition of vagally induced gastric tone, indicating activation of the GI-GI reflex. Under these conditions, about 17% of the hypothalamic points induced gastric excitation, due to withdrawal of sympathetic tone. The GI-GI reflex can thus be inhibited from diencephalic levels. This inhibition is not linked to any distinct cardiovascular 'pattern'.