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

1. Acid back-diffusion through a disrupted gastric mucosal barrier is known to increase gastric mucosal blood flow via a neural mechanism. The present study examined how the acid-evoked change in the gastric microcirculation compares with blood flow changes in the left gastric artery, one of the major arteries supplying the stomach, and whether the dilator mediators in the left gastric artery are identical to those in the gastric mucosa. 2. The experiments were performed on rats anaesthetized with urethane. Blood flow in the left gastric artery was measured by the ultrasonic transit time shift technique, and blood flow in the gastric mucosa was assessed by the hydrogen gas clearance method. 3. Gastric acid back-diffusion evoked by perfusion of the stomach with 15% ethanol in 0.15 M HCl increased blood flow in the left gastric artery by a factor of 4.7, which was significantly larger than the 2.9-fold increase in blood flow through the gastric mucosa. Blood pressure and heart rate were not altered appreciably. 4. The acid-evoked hyperaemia in the left gastric artery was left unaltered by atropine and the substance P receptor antagonist RP-67580. 5. The calcitonin gene-related peptide (CGRP) antagonist CGRP (8-37) had no effect on gastric blood flow but prevented the dilator action of CGRP and inhibited the acid-evoked hyperaemia in the gastric mucosa to a larger degree than the hyperaemia in the left gastric artery. 6. Blockade of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester (L-NAME) caused constriction of the left gastric artery and the gastric mucosal microvessels. The acid-evoked vasodilatation in the gastric mucosa was blocked by L-NAME, whereas the dilator response in the left gastric artery was not significantly depressed. 7. The data show that the gastric hyperaemic response to acid back-diffusion results from dilatation of mucosal microvessels and extramural arteries. The dilator mechanisms, however, differ between the two vascular beds. CGRP and nitric oxide are important vasodilator mediators in the gastric mucosa but are of less relevance in the left gastric artery.
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PMID:Vascular bed-dependent roles of the peptide CGRP and nitric oxide in acid-evoked hyperaemia of the rat stomach. 753 14

The goal of these studies was to examine the effects of substance P, a tachykinin neuropeptide, on pathways of microvascular permeability. Individual frog mesenteric venular capillaries were cannulated, and albumin apparent permeability coefficients (Ps) were determined by quantitative fluorescence microscopy. Ps of albumin (PsAlb) rose from 6.8 +/- 1.8 (SE) cm.s-1.10(7) at control to 22.3 +/- 2.3 cm.s-1.10(7) when substance P (10(-11) M) was perfused. The effect of increased microvessel permeability induced by substance P (10(-11) M) was blocked with the nonpeptide substance P receptor antagonist CP-96,345 and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. PsAlb increased 0.99 cm.s-1.10(7) for every cmH2O increase in microvessel pressure after treatment of the vessel with substance P, demonstrating coupling of albumin flux to transvascular water flow. In conclusion, the mechanism of increased microvessel permeability in response to substance P appears to be the result of receptor-mediated increase in nitric oxide production and formation of water-filled convective pathways presumably located between adjacent endothelial cells.
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PMID:Substance P increases microvascular permeability via nitric oxide-mediated convective pathways. 753 70

The effects of i.p. administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME) and its inactive isomer, D-NAME, were tested in two nociceptive paradigms in the rat. In the first paradigm, rats were lightly anaesthetized with a mixture of chloral hydrate (120 mg/kg, i.p.) and sodium pentobarbital (20 mg/kg, i.p.). Tail flick reaction times were monitored and thermal hyperalgesia was induced by immersion of the tail in hot water at 55 degrees C for 1.5 min. In the groups of rats pretreated with saline (n = 5), 100 mg/kg D-NAME (n = 6), 10 (n = 5) or 25 (n = 6) mg/kg L-NAME, this thermal injury induced a transient reduction in the reaction time that was 54-59% of the baseline value. However, in the groups of rats pretreated with 50 (n = 6) or 100 (n = 7) mg/kg L-NAME the reaction times were 73.9 +/- 2.7% (P < 0.05) and 102.3 +/- 0.9% (P < 0.001) of the baseline values respectively, indicating a block of the hyperalgesic responses seen in the other groups. As this hyperalgesia has been reported to be blocked by NK-1 receptor antagonists, it is suggested that it is due to the action of endogenous substance P. In the second paradigm, tail flick responses were monitored in the awake rat and thermal hyperalgesia was induced by intrathecal administration of substance P (6.5 nmol) via a chronically implanted catheter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Implication of a nitric oxide synthase mechanism in the action of substance P: L-NAME blocks thermal hyperalgesia induced by endogenous and exogenous substance P in the rat. 852 67

1. We have previously found that intrathecal administration of prostaglandins E2 (PGE2) and D2 (PGD2) into conscious mice induced hyperalgesia by the hot plate test. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice tacking NMDA receptor epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunits. 2. PGE2 induced hyperalgesia over a wide range of doses from 50 pg to 500 ng kg-1 in wild-type mice. But PGE2 could not induce hyperalgesia in epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunit knockout mice. 3. The NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), the non-NMDA receptor antagonist 7-D-glutamylaminomethyl sulphonic acid (GAMS), and the nitric oxide synthase inhibitor N epsilon-nitro-L-arginine methyl ester (L-NAME) inhibited the PGE2-induced hyperalgesia in wild-type mice. 4. PGD2 induced hyperalgesia at doses of 25 ng to 250 ng kg-1 in both wild-type and epsilon 1/epsilon 4 subunit knockout mice. The substance P receptor antagonist OP 96.345 blocked the PGD2-induced hyperalgesia in wild-type and epsilon 1/epsilon 4 subunit knockout mice. 5. These results demonstrate that the pathways leading to hyperalgesia are different between PGD2 and PGE2, and that both epsilon 1 and epsilon 4 subunits of the NMDA receptor are involved in the PGE2-induced hyperalgesia.
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PMID:Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor epsilon subunit knockout mice. 911 74

Repeated oesophageal acidification is a definitive feature of gastro-oesophageal reflux disease, which in turn is caused by relaxation of the lower oesophageal sphincter (LOS). This study in anaesthetised ferrets investigates the reflex pathways involved in effects of oesophageal acidification on motor function of the LOS, with particular focus on the role of tachykinins. LOS pressure was monitored with a perfused micromanometric sleeve assembly. Oesophageal acidification reduced LOS pressure by 48 +/- 5% until washout with saline. This reduction became larger with repeated tests, and was unaffected in amplitude by acute bilateral vagotomy, although the response became slower in onset. Intra-oesophageal capsaicin (0.5% solution) caused a 68 +/- 17% decrease in LOS pressure which remained unchanged with repeated tests. The NK-1 receptor antagonist CP96,345 (1-5 mg/kg intravenous (i.v.) blocked the post-vagotomy LOS responses to both intra-luminal acid and capsaicin. Close intra-arterial (i.a.) injections of capsaicin (1-100 micrograms) gut induced LOS relaxation which was neither vagally nor NK-1 receptor-mediated. Substance P or the selective NK-1 receptor agonist [Sar9, Met(O2)11] substance P (25-500 ng close i.a.) caused a biphasic LOS response, consisting of initial brief contraction followed by prolonged, dose-dependent relaxation. Tetrodotoxin (10 micrograms/kg close i.a.) changed the biphasic response to substance P to excitation only. The neurokinin-1 (NK-1) receptor antagonist CP96,345 (0.3-10 mg/kg i.v.) dose-dependently reduced the inhibitory response to substance P. The excitatory phase of the response to substance P was larger and prolonged after guanethidine (5 mg/kg, i.v.), or propranolol (1 mg/kg, i.v.). L-NAME (100 mg/kg i.v.) reduced the inhibitory phase. The selective NK-2 receptor agonist [beta-Ala8] neurokinin A(4-10) caused LOS excitation only. These data indicate that intra-oesophageal acid causes substance P release from extrinsic afferent nerve endings which activates local inhibitory pathways to the LOS via NK-1 receptors.
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PMID:Lower oesophageal sphincter responses to noxious oesophageal chemical stimuli in the ferret: involvement of tachykinin receptors. 940 24

Gallbladder motility is modulated by intrinsic nerves, the identities of which are not well established. The aim of this study was to determine the effect of nicotinic receptor stimulation of intrinsic nerves on gallbladder muscle contractility. Guinea pig gallbladder muscle strips were studied in vitro. Histamine 1 microM was used to increase baseline tone. The nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP), produced a biphasic response characterized by an initial transient contraction followed by a sustained relaxation. The initial contraction was inhibited by the neural blocker tetrodotoxin, the nicotinic antagonist hexamethonium, and the muscarinic antagonist atropine, but not by a substance P receptor antagonist or a bombesin receptor antagonist. The relaxation response to DMPP was not affected by tetrodotoxin, but was reduced by hexamethonium and omega-conotoxin GVIA, an inhibitor of neurotransmitter release. The relaxation response was reduced by the nitric oxide synthase inhibitor L-NAME, but not by a vasoactive intestinal peptide antagonist or propranolol. DMPP produces a biphasic response in the guinea pig gallbladder. The initial contractile response is mediated by nicotinic receptors on the cell body or axon of cholinergic nerves. The relaxation response appears to result, in part, from activation of nicotinic receptors on nerve terminals of nitric oxide-releasing nerves. These results suggest nicotinic receptors have heterogeneity in location depending on excitatory or inhibitory neuronal function.
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PMID:Investigation of endogenous neurotransmitters of guinea pig gallbladder using nicotinic agonist stimulation. 979 Apr 59

Streptozotocin (STZ)-induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy to assess the efficacies of potential analgesic agents. We have established this model, and here we question whether the changes in nocifensive reflex activity, used as a measure of hyperalgesia, are genuinely indicative of peripheral neuropathy or may rather be attributed to the extreme poor health of the animals. For comparison we have examined animals with peripheral neuropathy induced by partial ligation of the sciatic nerve. Diabetic animals were chronically ill, with reduced growth rate, polyuria, diarrhoea, and had enlarged and distended bladders. Indicative of their poor health, diabetic animals showed markedly reduced motor activity. In contrast, following partial sciatic nerve ligation rats showed none of these adverse effects and their motor activity was not different to naive animals. Diabetic animals displayed marked mechanical hyperalgesia, and some thermal hypoalgesia. Morphine and L-baclofen partially reversed established STZ-induced mechanical hyperalgesia, whilst the NK-1 receptor-antagonist RP-67580, the NMDA-antagonists MK801 and ketamine, and the nitric oxide synthase inhibitor L-NAME were without significant effect. Morphine and L-baclofen produced greater reversal of mechanical hyperalgesia following partial nerve ligation, although RP67580 and MK801 showed little or no activity. These data confirm previous findings that STZ-induced diabetes in rats produces long-lasting mechanical, but not thermal hyperalgesia. In our experience this mechanical hyperalgesia is largely resistant to a range of pharmacological tools. However, we feel that the profound ill-health of the animals, together with the poor activity of a range of potential analgesic drugs, must raise questions on the predictive value of these animals as a model for the human condition of chronic diabetic pain seen in patients receiving long-term insulin treatment, as well as ethical concerns on the use of the animals themselves.
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PMID:Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat. 1043 18

The effects of endotoxin on fecal pellet output and the neural mechanisms involved in this response were investigated in conscious rats. E. coli endotoxin (40 micro g/kg i.p.) significantly increased fecal excretion for 3 h after the injection. Water content in feces was not modified by endotoxin. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats prevented the stimulatory effect of endotoxin and so did abdominal vagotomy. Adrenoceptor blockade with phentolamine (5 mg/kg i.p.) + propranolol (3 mg/kg i.p.) did not modify pellet output in endotoxin-treated rats while muscarinic receptor blockade with atropine (1 mg/kg i.p.) abolished the stimulatory effect of endotoxin. Finally, the increase in pellet output induced by endotoxin was prevented in animals receiving the substance P receptor antagonist D-Pro2, D-Trp7,9-substance P (2 mg/kg i.p.) or the NO-synthase inhibitor L-NAME (10 mg/kg i.p.). None of the above treatments modified pellet output in saline-treated rats. These observations indicate that endotoxin increases fecal pellet output through a nervous reflex in which capsaicin-sensitive afferent neurons and the release of excitatory (acetylcholine and substance P) and inhibitory (NO) neurotransmitters in the colonic wall are involved.
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PMID:Endotoxin stimulates fecal pellet output in rats through a neural mechanism. 1261 41

In the present study the authors investigated if the inhibitory effect of leptin in the ovary was mediated via nitric oxide (NO) using human granulosa cells (GCs). Human GCs were obtained from preovulatory follicles of women who underwent IVF. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that human GCs expressed mRNA of leptin and mRNA of isoforms of leptin receptor, including one long form and two types of short forms. Exposure of human GCs to leptin at concentrations of 3-30 ng/ml for 60 min dose-dependently increased the fluorescence of 4,5-diaminofluorescein (DAF-2), an NO-sensitive dye. The effect of leptin on DAF-2 fluorescence was inhibited by pretreatment of human GCs with 100 microM nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase (NOS), indicating that the increase in DAF-2 fluorescence properly reflected the intracellular NO production. FSH (1 ng/ ml) and IGF-I (30 ng/ml) stimulated 17beta-estradiol (E2) production in human GCs, respectively. FSH plus IGF-I induced a further increase in E2 production. Leptin did not significantly alter basal or FSH-dependent E2 production, but it inhibited the effect of IGF-I on E2 production and the synergistic effect of IGF-I on FSH-stimulated E2 production. The inhibitory effect of leptin on IGF-I argumentation of E2 production was attenuated by pretreatment of human GCs with 100 microM L-NAME. In conclusion, leptin could induce NO production in human GCs. The inhibitory effect of leptin on IGF-I augmentation of E2 production in human GCs was attenuated by L-NAME, strongly suggesting that NO may mediate the action of leptin in human GCs.
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PMID:Nitric oxide mediates inhibitory effect of leptin on insulin-like growth factor I augmentation of 17beta-estradiol production in human granulosa cells. 1537 Dec 74

Parasympathetic vasodilatation in the rat submandibular gland is mediated by nitric oxide-dependent and -independent mechanisms (prostacyclin and endothelium-derived hyperpolarizing factor (EDHF)). The purpose of this study was to determine the influence of gender on the relative contributions of each pathway to nerve-stimulated vasodilatation. Absolute increases in perfusion (laser Doppler flowmetry) were similar in male and female rats (in arbitrary perfusion units: 6159+/-4530 and 5601+/-3877 at 2 Hz; 15645+/-6830 and 14848+/-6118 at 5 Hz; and 22418+/-7660 and 18878+/-5864 at 10 Hz). However, expressed as a percentage increase above resting values, stimulated perfusion was higher in males than in females (P<0.05). In males both Nomega-nitro-L-arginine methyl ester (L-NAME) and indomethacin partly blocked parasympathetic vasodilatation at all frequencies tested (P<0.05). In female rats significant reductions in nerve-stimulated perfusion were observed only at 2 and 5 Hz, but the effects of L-NAME were greater than in males (-64 compared with -45% at 2 Hz and -45 compared with -33% at 5 Hz, P<0.05). Indomethacin by itself had no apparent effect in females. The combined effects of L-NAME and indomethacin were dependent on the order of administration and on gender. Following L-NAME, indomethacin had no further effect in males or females. L-NAME reduced indomethacin-resistant vasodilatation in males and females, but the added effect of indomethacin was more pronounced in males. Finally, atropine-resistant vasodilatation was partly blocked by L-NAME, and the remaining vasodilatation was abolished by spantide I (substance P receptor antagonist). We conclude that NO, products of cyclo-oxygenase activity and EDHF all play a role in parasympathetic vasodilatation, but that NO and EDHF are the major endothelium-derived vasodilators in the rat submandibular gland. In addition, when other pathways are blocked EDHF makes a greater contribution in females. Lastly, both vasoactive intestinal peptide and substance P contribute to the atropine-resistant vasodilatation.
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PMID:The influence of gender on parasympathetic vasodilatation in the submandibular gland of the rat. 1636 82


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