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

The possible modulating effect of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), on cholinergic neurotransmission was assessed in longitudinal muscle strips of rat gastric fundus. VIP and NO are the putative co-transmitters of the inhibitory non-adrenergic non-cholinergic (NANC) neurones in this tissue. VIP concentration dependently inhibited cholinergic contractions induced by 2-min transmural stimulation, relaxed tissues, the tone of which was continuously raised by transmural stimulation, and shifted to the right the frequency-response curves for contraction induced by transmural stimulation with a cumulative increase of frequency. The same effect was found when contractions were induced with methacholine, suggesting that only functional antagonism at the postsynaptic smooth muscle cell level is involved. On 30-min incubations, 3 x 10(-4) M NG-nitro-L-arginine methyl ester (L-NAME) potentiated cholinergic responses to 20-s transmural stimulation, while not influencing contractions of similar amplitude evoked by methacholine; the cholinergic responses to 2-min transmural stimulation were also not influenced. The potentiating effect of L-NAME was prevented by L-arginine but not D-arginine. These results suggest that endogenous NO released from the inhibitory NANC neurones during short trains of transmural stimulation interferes with cholinergic neurotransmission either by functional antagonism of acetylcholine at the postsynaptic level or by presynaptic inhibition of acetylcholine release.
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PMID:Influence of vasoactive intestinal polypeptide and NG-nitro-L-arginine methyl ester on cholinergic neurotransmission in the rat gastric fundus. 133 Jun 23

1. The nitric oxide (NO) synthesis inhibitors NG-monomethyl L-arginine (L-NMMA) and L-nitroarginine methyl ester (L-NAME) reduced relaxations of guinea-pig tracheal smooth muscle elicited by stimulation of intramural non-adrenergic, non-cholinergic (NANC) nerves, but D-NMMA had no effect. L-NAME was 10-30 times more potent than L-NMMA. Relaxations produced by sodium nitroprusside and vasoactive intestinal polypeptide (VIP) were not affected by L-NMMA or L-NAME. 2. The inhibitory effect of L-NMMA on NANC-mediated relaxations was partially reversed by L-arginine but was not affected by D-arginine. 3. VIP antibody and alpha-chymotrypsin abolished or greatly reduced the relaxant action of VIP and reduced relaxations elicited by stimulation of NANC nerves; the residual NANC relaxation was further reduced by L-NAME. 4. The results suggest that NO and VIP are mediators of NANC-induced relaxations of guinea-pig tracheal smooth muscle. We propose the term 'nitrergic' to describe transmission processes which are mediated by NO.
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PMID:Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide. 204 35

1. Changes in isometric tension were recorded from circular muscle strips of rat pyloric sphincter in vitro, in response to electrical field stimulation and exogenously applied muscle relaxants. 2. Concentration-response relationships were studied for relaxation to exogenously applied adenosine 5'-triphosphate (ATP) and two analogues, 2-methylthioATP (2-MeSATP) and alpha,beta-methylene ATP (alpha,beta-MeATP). These drugs evoked concentration-dependent relaxation of rat pyloric sphincter with an order of potency 2-MeSATP > ATP >> alpha,beta-MeATP, indicating the presence of P2y-purinoceptors. The IC50 value of each nucleotide was: 2-MeSATP, 5.0 x 10(-8); ATP, 7.9 x 10(-6) M; alpha,beta-MeATP showed only slight activity at a concentration of 0.1 mM. 3. Frequency-response relationships for relaxations evoked by electrical field stimulation (EFS) were studied in the absence and presence of 10 microM NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO) synthesis) and 20 microM reactive blue 2 (a P2y-purinoceptor antagonist). It was found that these substances significantly reduced the relaxant response of rat pyloric sphincter to EFS by 40% and 50% respectively. In the presence of both L-NAME and reactive blue 2 the responses were reduced by 75%. 4. Concentration-response relationships were studied for ATP and 2-MeSATP in the presence of L-NAME. It was found that L-NAME did not significantly inhibit the relaxant responses to these drugs. 5. Concentration-response relationships for ATP and noradrenaline were studied in the presence of reactive blue 2 (20 microM); the P2y-antagonist significantly inhibited the relaxant response to ATP, but not that to noradrenaline. 6. The distribution of nitric oxide synthase in rat pyloric sphincter was investigated immunohistochemically,with immunoreactive nerve fibres found throughout the circular muscle layer and myenteric plexus of the sphincter.7. While abundant vasoactive intestinal polypeptide (VIP)-containing nerve fibres were demonstrated immunohistochemically in the pyloric sphincter, relaxations to VIP (1 nM-0.3 micro M) were not observed in this preparation.8. It is concluded that ATP, acting through P2y-purinoceptors, and NO contribute to NANC inhibitory neurotransmission in rat pyloric sphincter. NO appeared to contribute to the later component of NANCrelaxation. The action of ATP was not mediated by NO, and VIP did not contribute to the NANCinhibitory responses in this preparation.
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PMID:Contribution of ATP and nitric oxide to NANC inhibitory transmission in rat pyloric sphincter. 753 79

A possible mechanism for the nicotine-induced relaxation of circular muscle strips of the guinea-pig gastric fundus was investigated. In the presence of atropine (0.2 microM), nicotine produced concentration-dependent relaxation with a maximum effect at 100 microM (mean pEC50 value, 4.60). The maximum relaxation due to nicotine was greatly reduced by pretreatment with tetrodotoxin (0.3 microM) or hexamethonium (10 microM), but not with metitepine (0.3 microM). Combined pretreatment with timolol (0.3 microM) and phentolamine (0.3 microM) or chemical sympathectomy by 6-hydroxydopamine pretreatment partially inhibited the nicotine-induced relaxation. alpha-Chymotrypsin (2 u/ml) which abolished the equivalent relaxation induced by vasoactive intestinal polypeptide (VIP) had no effect on nicotine-induced relaxation. NG-Nitro-L-arginine (L-NNA) and NG-Nitro-L-arginine methyl ester (L-NAME) caused a concentration-dependent inhibition of the nicotine-induced relaxation (98% inhibition at 10 microM of L-NNA), but had no effect on sodium nitroprusside- or noradrenaline-induced relaxation. The inhibitory effect of L-NNA or L-NAME was reversed completely by L-arginine (3 mM), but not by D-arginine (3 mM). From these results, we concluded that nicotine-induced relaxation of the guinea-pig gastric fundus is mediated largely by the release of nitric oxide or a related substance and partially by the release of noradrenaline. Possible contributions of 5-hydroxytryptamine or VIP to the nicotine-induced relaxation appear to be negligible.
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PMID:Investigation of nicotine-induced relaxation of circular smooth muscle of the guinea-pig gastric fundus. 769 61

1. Regional haemodynamic responses to the homologous peptides, pituitary adenylate cyclase-activating peptide (1-27) (PACAP27) and vasoactive intestinal polypeptide (VIP) were assessed by giving 20 min infusions (1.5-15 nmol kg-1 h-1) in conscious, chronically-instrumented, Long Evans rats. 2. PACAP27 caused dose-dependent depressor and tachycardic effects associated with renal, mesenteric and hindquarters vasodilatations, although only in the latter vascular bed was there a sustained increase in flow. 3. VIP caused dose-dependent depressor and tachycardic effects that were not significantly different from those caused by equimolar doses of PACAP27. However, the hindquarters vasodilator effects of VIP (at 7.5 and 15 nmol kg-1 h-1) were greater than those of PACAP27 (at the same doses), and accompanied by reductions in renal and mesenteric flows and conductances. 4. In the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 11 mumol kg-1 h-1), there was significant inhibition of the hindquarters vasodilator effects of PACAP27 and VIP (at 7.5 and 15 nmol kg-1 h-1). Under these circumstances the renal and mesenteric vasoconstrictor effects of VIP were abolished. 5. The beta 2-adrenoceptor antagonist, ICI 118551 (670 nmol kg-1 bolus, 335 nmol kg-1 h-1 infusion), reduced the matched hindquarters vasodilator responses to PACAP27 (15 nmol kg-1 h-1) and VIP (7.5 nmol kg-1 h-1), and also abolished the renal vasoconstrictor effects of VIP. 6. The AT1-receptor antagonist, losartan potassium (20 mumol kg-1), had no significant effect on the haemodynamic response to PACAP27 (15 nmol kg-1 h-1), but augmented the hypotensive action of VIP (7.5 nmol kg-1 h-1). This influence of losartan was associated with conversion of the renal and mesenteric vasoconstrictor effect of VIP to vasodilatation. 7. Our findings show that similar changes in mean systemic arterial blood pressure in response to PACAP27 and VIP conceal substantial differences in their regional haemodynamic actions. Although the hindquarters vasodilator effects of both peptides involve NO- and Beta2-adrenoceptor-mediated mechanisms,it appears that activation of the renin-angiotensin system contributes significantly to the haemodynamic effects of VIP, but not to those of PACAP27.
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PMID:Regional haemodynamic responses to pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide in conscious rats. 791 21

Calcitonin gene-related peptide (CGRP) is a novel polypeptide that exerts important effect on the cardiovascular system through its vasorelaxant properties. We studied in vivo in normal rats the effect of acute administration of CGRP on whole kidney function and showed that the intravenous infusion of the peptide resulted in a fall of blood pressure associated with a marked increase in renal plasma flow (RPF) as well as glomerular filtration rate (GFR). These changes were reversible with discontinuation of CGRP infusion. To evaluate whether the renal hemodynamic responses to the peptide were mediated by endogenous vasodilatory prostaglandins of endothelial origin, animals were preexposed to indomethacin, a cyclooxygenase enzyme inhibitor. Inhibition of prostaglandins synthesis with indomethacin failed, however, to prevent the increase in RPF and GFR observed during CGRP infusion. By contrast, NG-nitro-L-arginine methyl ester (L-NAME), which inhibits the synthesis of nitric oxide, a newly discovered endothelium-derived relaxing factor, completely abolished the renal hemodynamic changes induced by CGRP. Moreover, L-arginine infusion in L-NAME-treated rats restored the renal response to CGRP. We have also shown that systemic infusion of CGRP progressively normalized RPF and GFR that were reduced in response to a bolus intravenous injection of the vasoconstrictor endothelin-1. This indicates that CGRP regulates renal hemodynamics and modulates the deleterious effects of vasoconstrictive substances on the kidney.
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PMID:Calcitonin gene-related peptide reduces renal vascular resistance and modulates ET-1-induced vasoconstriction. 797 88

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

Formation of NO, enzymatically catalyzed by NO synthases in both endothelial cells and autonomic nerves, seems to explain some noncholinergic nonadrenergic tissue reactions. We studied the possible role of NO in vagally induced pancreatic exocrine secretion using isolated perfused porcine pancreas (n = 11) with intact vagus nerve (VN) supply. Electrical stimulation of the VN (8 Hz, 10 mA) and infusions of vasoactive intestinal polypeptide (VIP, 2 x 10(-9) M) were carried out before and after addition to the perfusate of the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or NG-nitro-L-arginine (L-NNA, 10(-5) M) with and without further addition of L-arginine (10(-3) M). We also studied the effects of L-arginine alone and of sodium nitroprusside (10(-4) M). In all experiments VN and VIP caused a profuse exocrine secretion (43 +/- 7 and 44 +/- 11 times basal secretion). The inhibitors increased vascular resistance approximately twofold but had no effect on the vascular relaxation caused by VIP and VN. The exocrine fluid response to VN was reduced to 19 +/- 5 and 4.7 +/- 1.8% (L-NAME and L-NNA), and response to VIP was reduced to 54 +/- 12 and 35 +/- 13%. Protein and bicarbonate outputs largely paralleled flow rate. Addition of L-arginine (no effects alone) to L-NAME restored the responses to VN (to 100 +/- 21% of controls) and increased VIP responses (to 65 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of nitric oxide in neurally induced pancreatic exocrine secretion in pigs. 814 Dec 93

1. Calcitonin gene-related peptide (CGRP) potently enhances mucosal blood flow in the rat stomach. The aim of this study was to examine whether CGRP also dilates extramural arteries supplying the stomach and whether the vasodilator action of CGRP involves nitric oxide (NO). 2. Rat CGRP-alpha (0.03-1 nmol kg-1, i.v.) produced a dose-dependent increase in blood flow through the left gastric artery (LGA) as determined by an ultrasonic transit time technique in urethane-anaesthetized rats. Blockade of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 20 and 60 mumol kg-1, i.v.) significantly reduced basal blood flow (BF) in the LGA and attenuated the hyperaemic activity of CGRP by a factor of 2.8-4. D-NAME tended to enhance basal BF in the LGA but had no influence on the dilator activity of CGRP. The ability of vasoactive intestinal polypeptide to increase left gastric arterial blood flow remained unaltered by L-NAME. 3. L-NAME (20 and 60 mumol kg-1, i.v.) evoked a prompt and sustained rise of mean arterial blood pressure (MAP) and caused a slight decrease in the hypotensive activity of CGRP. In contrast, D-NAME induced a delayed and moderate increase in MAP and did not influence the hypotensive activity of CGRP. 4. Rat CGRP-alpha dilated the isolated perfused bed of the rat LGA precontracted with methoxamine and was 3 times more potent in this respect than rat CGRP-beta. The dilator action of rat CGRP-alpha in this preparation was not affected by L-NAME or D-NAME (40 microM). 5. L-NAME (60 micromol kg-1, i.v.) reduced gastric mucosal blood flow as assessed by laser Doppler flowmetry and diminished the hyperaemic activity of rat CGRP-alpha in the gastric mucosa by a factor of 4.5, whereas D-NAME was without effect.6. These data show that CGRP is a potent dilator of mucosal and extramural resistance vessels in the rat stomach. Its dilator action involves both NO-dependent and NO-independent mechanisms.
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PMID:Nitric oxide-dependent and -independent hyperaemia due to calcitonin gene-related peptide in the rat stomach. 822 Sep 1

1. The extent to which parasympathetic vasodilator responses, in the submandibular gland of the cat, depend upon release of nitric oxide related (NO chi) or endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anesthetized cats given N omega-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine. 2. Close intra-arterial infusions of L-NAME (> or = 100 mg kg-1) produced a steady and significant rise in mean aortic pressure together with a steady increase in basal submandibular vascular resistance over the next 20-30 min, which persisted thereafter. 3. In cats pretreated with propranolol, to block beta-adrenoceptor-mediated vasodilatation, salivation and vasodilatation in response to stimulation of the chorda-lingual nerve were reduced but not abolished by L-NAME (> or = 100 mg kg-1, I.A.). Subsequent administration of atropine (> or = 1 mg kg-1 I.V.) completely suppressed the secretory response and virtually eliminated the vascular response. 4. In cats pretreated with atropine (> or = 1.0 mg kg-1 I.V.) administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the vasodilator response to chorda-lingual stimulation at 2 Hz continuously, or at 20 Hz for 1 s at 10 s intervals. 5. Administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the submandibular vasodilator response to infusions of VIP (10 and 20 ng I.A.) and significantly reduced, but did not abolish that to acetylcholine (100 ng min-1 I.A.). 6. These results provide further support for the view that both acetylcholine and vasoactive intestinal polypeptide-like immunoreactivity (VIP) are released from the postganglionic parasympathetic nerve terminals and produce effects on the blood vessels in submandibular glands of the cat. They also provide evidence for a direct vascular action of acetylcholine, independent of NO chi, but VIP appears to act indirectly via NO chi formation.
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PMID:Nitric oxide-related vasodilator responses to parasympathetic stimulation of the submandibular gland in the cat. 822 8


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