UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether the release of endothelium-derived relaxing factor (EDRF) is sympathetically mediated, we studied the effects of beta-blockade by propranolol, ganglionic blockade with hexamethonium, or mechanical pithing on the blood pressure response to EDRF inhibition in anesthetized rats. We inhibited EDRF with 10 mg/kg of either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine-methyl ester (L-NAME). In controls, L-NMMA and L-NAME increased blood pressure by 14 +/- 1 (p less than 0.01) and 22 +/- 2 mm Hg (p less than 0.01), respectively. Propranolol lowered blood pressure from 98 +/- 3 to 72 +/- 4 mm Hg without altering the response to L-NAME (delta 26 +/- 3). This response correlated with the resting blood pressure (r = 0.87; p less than 0.001). Hexamethonium (25 mg/kg) lowered blood pressure from 118 +/- 6 to 85 +/- 4 mm Hg but did not change the response to L-NMMA (delta 15 +/- 1). In pithed rats, blood pressure was lowered, but the pressor response to L-NAME was unchanged. When blood pressure was returned to normotensive levels by angiotensin II, norepinephrine, or phenylephrine, L-NAME increased blood pressure by 50 +/- 2, 68 +/- 8, and 109 +/- 7 mm Hg, respectively (p less than 0.001). We conclude that an intact autonomic nervous system is not needed for the pressor response to EDRF inhibition. The enhanced response in pithed rats treated with vasoconstrictors may be due to removal of the buffering effect of the baroreceptors and the absence of EDRF, which would oppose vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sympathetic modulation of endothelium-derived relaxing factor. 135 May 73

To evaluate if L-arginine-nitric oxide-pathways are involved in the neural relaxation of the sphincter of Oddi, we studied the effect of nitric oxide synthase inhibition on electrical field stimulation-induced relaxation of the sphincter of Oddi in the guinea pig in vitro. After incubation with atropine (1 microM), phentolamine (1 microM) and propranolol (1 microM), histamine (50 microM) and cholecystokinin-octapeptide (25 nM) produced similar increases in sphincter tone. Subsequent field stimulation induced sphincteric relaxation, that was significantly greater when the initial tone had been raised by cholecystokinin (5 Hz, 59 +/- 9%; 10 Hz, 79 +/- 9%) compared to histamine (5 Hz, 27 +/- 3%; 10 Hz, 40 +/- 7%). N-omega-Nitro-L-arginine methyl ester (L-NAME, 100 microM), which competitively inhibits nitric oxide synthase, markedly suppressed this relaxation. The subsequent addition of L-arginine (1 mM), but not D-arginine (1 mM), restored the relaxation. Hexamethonium (100 microM) did not affect the relaxation, but tetrodotoxin (1 microM) completely abolished it. Sodium nitroprusside caused a dose-dependent relaxation of the sphincter (ED50 13 nM), which was unaffected by L-NAME. In conclusion, endogenous nitric oxide synthase products represent a major transmitter of non-adrenergic non-cholinergic relaxation of the sphincter of Oddi in the guinea pig. This relaxation is partially facilitated by cholecystokinin.
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PMID:Involvement of L-arginine-nitric oxide pathways in neural relaxation of the sphincter of Oddi. 768 81

1. The effects of inhibiting nitric oxide (NO)-synthase on fluid transport, mucosal cyclic GMP and cyclic AMP levels and intraluminal prostaglandin E2 (PGE2)-release were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Experiments were performed under basal conditions as well as under conditions, when net fluid secretion was induced by Escherichia coli heat stable enterotoxin a (E. coli STa) or PGE2. 2. Intravenous infusion of the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 0.25-50 mg kg-1, 45 min) dose-dependently reversed net fluid absorption to net secretion, whereas infusion of D-NAME, the inactive enantiomer of L-NAME, in corresponding doses did not influence net fluid transport. N omega-nitro-L-arginine (L-NOARG, 25 mg kg-1), another NO-synthase inhibitor, also elicited net secretion of fluid. 3. L-NAME (25 mg kg-1)-induced net fluid secretion was reversed to net absorption by infusion of L-arginine (400 mg kg-1) or sodium nitroprusside (1 mg kg-1) and s.c. administration of indomethacin (10 mg kg-1). Hexamethonium (1 mg kg-1, s.c.), a ganglionic blocker and granisetron (100 micrograms kg-1, s.c.), a 5-HT3-receptor antagonist, did not influence L-NAME-induced net secretion. 4. Net fluid secretion induced by intraluminal instillation of E. coli STa (10 units ml-1) was enhanced by infusion of L-NAME (25 mg kg-1) and was inhibited by infusion of L-arginine (400 mg kg-1) and sodium nitroprusside (1 mg kg-1). D-Arginine (400 mg kg-1) did not influence E. coli STa-induced fluid secretion. Likewise, net fluid secretion induced by i.a. infusion of PGE2 (79 ng ml-1, 30 min) was enhanced by infusion of L-NAME and was inhibited by L-arginine and sodium nitroprusside. D-Arginine(400 mg kg-1) did not influence PGE2-induced fluid secretion.5. PGE2 levels in intraluminal fluid were not elevated after infusion of L-NAME (25mgkg-1) compared to controls.6. Mucosal cyclic GMP and cyclic AMP levels after L-NAME-treatment were not different from control values.7. These results indicate that nitric oxide plays an important role in the regulation of intestinal fluid transport. The data suggest a nitric oxide-dependent proabsorptive tone in the intestine, which possibly involves the enteric nervous system and suppression of prostaglandin formation. This proabsorptive tone also may downregulate fluid secretion induced by E. coli STa or PGE2.
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PMID:Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo. 771 8

Treatment 20 min beforehand with an inhibitor of nitric oxide (NO) synthesis NW-nitro-1-arginine methyl ester (L-NAME) (12.5, 25, 50 or 100 mg/kg, s.c.), dose-dependently intensified gastric glandular mucosal ulceration produced by cold-restraint stress. Hexamethonium (20 mg/kg) or atropine (1 mg/kg) pretreatment s.c. 20 min before stress strongly antagonised stress-evoked ulceration, as well as the ulcer-potentiating effects of L-NAME when either cholinoceptor antagonist was given concurrently with the NO inhibitor. Stress-induced mast cell degranulation was not worsened by L-NAME pretreatment. The findings suggest that NO could confer partial protection against stress-induced gastric ulcer formation; its activity is triggered off by the ulcerogenic mechanism of stress.
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PMID:Nitric oxide inhibition intensifies cold-restraint induced gastric ulcers in rats. 809 77

Perfusion with ([N-Me-Phe3,D-Pro4]morphiceptin (PL017)), [D-Pen2,5]enkephalin (DPDPE) and MEt5 and Leu5 enkephalin induced circular muscle contractions and decreased immunoreactive vasoactive intestinal polypeptide (VIP) venous output in canine ileal segments. Motility and VIP responses to PL017 were abolished by the mu antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) and unchanged by the delta antagonist ICI 174,864 ([N,N-dially-Tyr1,Aib2,3]Leu-enkephalin) which abolished DPDPE motility and VIP responses. The VIP response to DPDPE was unchanged by CTAP, which reduced motility responses, suggesting a DPDPE interaction with endogenous mu opioids, at a mu/delta(complexed) receptor. ICI 174,864 abolished Met5 and Leu5 enkephalin motility responses and Leu5 enkephalin VIP responses while CTAP was ineffective on Leu5 enkephalin motility responses or on both enkephalin VIP responses. CTAP increased Met5 enkephalin motility responses suggesting mu actions to inhibit excitatory nerves. ICI 174,864 reduced Met5 enkephalin VIP output decrements requiring CTAP addition for abolition, suggesting actions at mu/delta(complexed) receptors. Inhibition of nitric oxide synthase with N-omega-L-arginine methyl ester (L-NAME) abolished delta opioid and reduced by 30% mu opioid motility responses, leaving the VIP response intact. Hexamethonium and atropine abolished tonic VIP output, leaving intact motility responses to PL017 and DPDPE. Subsequently L-NAME eliminated delta opioid and reduced by 1/3 mu opioid motility responses. All opioids reduced the NO-mediated IJPs in myenteric plexus-free ileal circular muscle. Thus mu or delta opioids inhibit both NO and VIP release but removal of NO, not VIP, disinhibits circular muscle motility.
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PMID:Identification of mechanisms and sites of actions of mu and delta opioid receptor activation in the canine intestine. 811 80

In chickens CCK-8s induces defecation and causes an inhibition of rectal electrical activity (EA) and an increase in cecal motility. In contrast, CCK-4 inhibits the motility of both rectum and ceca. The cecorectal responses to CCK-8s and CCK-4, given intravenously (i.v.), were studied in conscious chickens prepared with electrodes for electromyography; the influence of atropine, phentolamine plus propranolol, hexamethonium and L-NAME on such responses was determined. Atropine and phentolamine plus propranolol did not cause any change in the response to CCK-8s or CCK-4 in the cecorectal area. Hexamethonium only induced a significant decrease in the number of defecations (ND) induced by CCK-8s. L-NAME slightly modified the decrease in rectal EA due to CCK-8s. The effects of intracerebroventricular (i.c.v.) administration of CCK-8s and CCK-4 were also studied. CCK-8s and CCK-4, given i.c.v., caused, in conscious chickens, a slight decrease in cecal EA, in the 15 minutes following administration. This effect was similar to that seen after i.v. administration of CCK-4. In conclusion, our results suggest that the inhibitory action of CCK on chicken rectum is mediated, at least in part, through nitric oxide release. In addition, nicotinic receptors mediate the increase in the ND caused by CCK-8s. Ganglionic, muscarinic, adrenergic and nitrergic blockade were not able to modify the excitatory cecal response to CCK-8s, which may indicate that the receptor mediating this effect is located on the cecal smooth muscle. Finally, the inhibitory action of i.v. CCK-4 on chicken cecum seems to be centrally mediated, as suggested by the fact that i.c.v. administration of either CCK-8s or CCK-4 induce a similar effect.
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PMID:Central and NO mediated mechanisms are involved in the inhibitory effects of CCK on the chicken cecorectal area. 863 13

In urethane-anaesthetized rats, moderate colonic distention (0.5 ml) induced reflex rhythmic contractions (5 mm Hg amplitude and 1.1 cycles/min frequency). Senktide (1-10 nmol/kg, i.v.), a tachykinin NK3 receptor selective agonist, transiently suppressed distension-induced contractions. SR 142,801 (1-10 mumol/kg i.v.), a non-peptide tachykinin NK3 receptor antagonist, had no effect on distension-induced contractions but prevented the inhibitory effect of senktide. Infusion of N-omega-nitro-1-arginine methyl esther hydrochloride (L-NAME, 20 mumol/ml/h, i.v) increased the amplitude of colonic contractions and decreased the inhibitory effect of senktide. Hexamethonium (15 mumol/ml/h, i.v.) or atropine (1 mumol/ml/h, i.v.) inhibited the distension-induced contractions. In hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and selectively enhanced the amplitude of contractions. Also SR 142,801 (10 mumol/kg), but not its inactive enantiomer SR 142,806, increased both amplitude and frequency of contractions. During continuous infusion of L-NAME and hexamethonium or atropine both frequency and amplitude of distension-induced colonic contractions were higher than when in hexamethonium or atropine only. Senktide (10 nmol/kg) had no effect and SR 142,801 (10 mumol/kg) produced a slight enhancement of colonic contractions. Infusion of sodium nitroprusside (3 mumol/ml/h, i.v.) decreased amplitude and frequency of distension-induced contractions. SR 142,801 had no effect in the presence of the nitric oxide (NO) donor. We conclude that tachykinins acting through NK3 receptors exert at least four different actions on colonic motility activated by distension: 1) a hexamethonium-resistant, NO-dependent, suppressant effect on contractions; 2) a hexamethonium-sensitive, NO-independent inhibitory effect on the amplitude of contractions; 3) a hexamethonium-resistant, NO-independent inhibitory effect on the amplitude of contractions and 4) a hexamethonium resistant and L-NAME-sensitive excitatory effect on amplitude of contractions. The prevalent inhibitory effect evoked in normal conditions along with the excitatory activity induced by SR 142,801 on hexamethonium-resistant colonic motility indicates that tachykinins, acting through neuronal NK3 receptors, activate NO-dependent and NO-independent inhibitory neurotransmission in the rat colon.
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PMID:In vivo evidence for the involvement of tachykinin NK3 receptors in the hexamethonium-resistant inhibitory transmission in the rat colon. 873

We studied the role of nitric oxide and inhibitory non-adrenergic, non-cholinergic (i-NANC) nerves in the regulation of airway responsiveness in anesthetized and mechanically ventilated cats. Vagal stimulation caused marked bronchodilation in the cats with sustained bronchoconstriction in the presence of atropine and propranolol. The bronchodilation evoked by vagal stimulation was completely abolished by hexamethonium (2 mg/kg). L-NG-nitroarginine methyl ester (L-NAME; 8 mg/kg + 2 mg/kg/min) significantly suppressed the relaxation evoked by vagal stimulation; the effect was particularly noticeable soon after the stimulation. Hexamethonium significantly increased airway responsiveness to serotonin: the PC200 decreased from 0.346 mg/ml (GSEM 1.23) without hexamethonium to 0.44 mg/ml (GSEM 1.63) with hexamethonium (p < 0.05). L-NAME shifted the dose-response curve to serotonin significantly to the left: the PC200 decreased from 0.261 mg/ml (GSEM 1.,40) without L-NAME to 0.056mg/dl (GSEM 1.38) with L-NAME (p < 0.05). Inhalation of citric acid (20%) caused marked bronchodilation during serotonin-induced bronchoconstriction. This bronchodilation occurred in the presence of atropine and propranolol and was inhibited by hexamethonium, therefore it was probably caused by a reflex mediated by i-NANC nerves. Furthermore, the bronchodilation induced by i-NANC nerves was significantly suppressed by L-NAME. These results suggest that nitric oxide is an important i-NANC transmitter that can modulate airway responsiveness.
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PMID:[Inhibitory non-adrenergic, non-cholinergic nerves and nitric oxide]. 875 2

1. We have described and analysed the movements of the isolated stomach during distension by correlating intragastric pressure with video recordings, and investigated the presence of intrinsic inhibitory and excitatory reflexes. 2. Isolated guinea-pig stomachs, placed in an organ bath, were slowly distended with Krebs solution using a syringe pump via a cannula through the pylorus. The changes in intragastric pressure during cycles of distension were monitored by pressure transducers connected to both oesophageal and pyloric cannulae. The resistivity of the gastric wall (change in pressure with volume, delta P/delta V) and the amplitude and frequency of phasic pressure events were calculated from pressure recordings. 3. The movements of the stomach were also recorded onto videotape. The motion of the gastric wall during distension cycles was analysed to establish the patterns of contractions, their propagation and the distribution of fluid in the stomach. During filling, fluid was preferentially accommodated in the fundus. Propagating (peristaltic) contractions, often starting in the fundus, moved aborally towards the pylorus. The peak of the phasic pressure event was observed when a contraction reached the orad antrum. As it reached the pylorus, intragastric pressure was at its minimum. 4. During the initial phase of distension, intragastric pressure increased steeply. Tetrodotoxin and hyoscine reduced both the resistivity and amplitude of phasic pressure events. Hexamethonium had a similar effect. Thus distension appears to activate an excitatory reflex pathway, involving nicotinic ganglionic transmission. This reflex increases wall tension and enhances myogenic peristaltic contractions. 5. In control preparations, with larger distension volumes, the intragastric pressure decreased, despite the continued infusion of Krebs solution. L-NAME and apamin abolished this drop in pressure, indicating that gastric enteric inhibitory mechanisms prevail at larger distension volumes. After blockade of the excitatory reflex, hexamethonium antagonized the inhibitory response, indicating that activation of inhibitory mechanisms involves nicotinic transmission, probably on enteric inhibitory motoneurons. 6. Both the excitatory and inhibitory reflexes in the isolated stomach operate within a physiological range of gastric volumes. The excitatory reflex predominates at small distension volumes, leading to large phasic propagated contractions that mix the contents and may lead to emptying of the stomach. The inhibitory reflex, described previously as adaptive relaxation, can maximally relax the stomach and is activated preferentially at higher distension volumes to accommodate the contents. The interplay of these reflex pathways in the isolated stomach produces a rich repertoire of gastric movements. 7. The isolated stomach preparation, used with a combination of kinematic, kinetic and pharmacological methods, provides a highly suitable means of investigating the mechanisms of gastric motility.
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PMID:Excitatory and inhibitory motor reflexes in the isolated guinea-pig stomach. 917 3

This study has investigated the relative involvement of cholinergic, adrenergic, nitric oxide and tachykininergic transmission in extrinsic neural influences on the lower oesophageal sphincter (LOS) in urethane anaesthetized ferrets. A micromanometric assembly (OD 1.75 mm) incorporating a sleeve sensor was used for high-fidelity oesophageal, LOS and gastric pressure measurement at low perfusion rates (< 0.1 ml/min). The LOS response to vagal and splanchnic nerve stimulation (0.5 ms pulse width, 10 s duration) was frequency- and voltage-dependent. LOS responses to stimulation at 20 V, 10 Hz were investigated in separate groups of animals with either L-NAME (100 mg/kg), hexamethonium (15 mg/kg), guanethidine (5 mg/kg), CP96,345 (NK-1 antagonist, 4 mg/kg), atropine (0.4 mg/kg) or propranolol (1 mg/kg). Propranolol treatment was followed by yohimbine (1 mg/kg) and prazosin (0.25 mg/kg). Vagal stimulation caused an immediate decrease in LOS pressure, followed by increase on cessation of stimulation, followed by a prolonged decrease (77 +/- 2%) for up to 5 min. L-NAME did not affect inhibition, but increased excitation 4-fold (p < 0.001). Guanethidine and CP96,345 had no major effect. Hexamethonium decreased the inhibitory (p < 0.05) and excitatory (p < 0.01) responses. Atropine reduced the excitatory response (p < 0.05). Some inhibition still remained if all treatments were combined. Splanchnic stimulation reduced LOS pressure by 70 +/- 6% for 101 +/- 17 s. L-NAME, guanethidine, hexamethonium and CP96,345 all independently significantly reduced inhibition. The combination of guanethidine and CP96,345 usually abolished splanchnic-induced inhibition. Atropine was without effect. Propranolol (1 mg/kg) changed the splanchnic-induced response from mainly inhibition to excitation (100 +/- 44% increase). LOS responses to noradrenaline (1-10 micrograms close IA) showed similar features to responses to splanchnic stimulation. We conclude that vagal stimulation evokes LOS relaxation via activation of established cholinergic and NANC mechanisms and other, unidentified mechanisms. Splanchnic stimulation activates adrenergic neurones probably via nicotinic and non-nicotinic ganglionic mechanisms, which in turn elicit beta adrenergic inhibitory effects on the LOS. Splanchnic stimulation also antidromically activates spinal afferent fibres. These may release substance P from peripheral myenteric plexus and prevertebral ganglionic endings causing activation of myenteric NANC inhibitory neurones and sympathetic neurones, respectively.
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PMID:Vagal and sympathetic influences on the ferret lower oesophageal sphincter. 940 23

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