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)

1. The nature of neurotransmitter(s) involved in non-adrenergic non-cholinergic (NANC) relaxations induced by electrical stimulation (10 s trains, 1-8 Hz) was investigated in the precontracted longitudinal muscle-myenteric plexus preparation of the rat ileum. 2. Electrical stimulation of the tissue induced complex responses, consisting of a primary contraction, a primary relaxation, an off-relaxation and a rebound contraction, which were all tetrodotoxin(TTX)-sensitive. 3. Vasoactive intestinal polypeptide (VIP) and carbon monoxide (CO) did not induce relaxations. alpha-Chymotrypsin did not reduce the relaxations induced by electrical stimulation, while zinc protoporphyrin IX had non-specific effects. 4. Nitric oxide (NO) induced concentration-dependent relaxations. NG-nitro-L-arginine methylester (L-NAME) abolished the primary contractions and off-relaxations, while it partially reduced the primary relaxations. 5. ATP induced relaxations and ATP-desensitization of the tissues partially reduced the primary relaxations. Suramin and reactive blue 2 did not consistently influence the primary relaxations. 6. The ATP-induced relaxations were not influenced by L-NAME or TTX. The inhibitory effect of ATP-desensitization and L-NAME did not summate. 7. The cyclic AMP content of the tissue did not increase upon electrical stimulation or after addition of NO or ATP. The cyclic GMP content of the tissue increased upon electrical stimulation and addition of NO, but not after addition of ATP. 8. It is concluded that the relaxation induced by electrical stimulation consists of two types of responses. The off-relaxation is completely nitrergic, while the primary relaxation is mediated by NO, ATP and an as yet unknown transmitter which is not VIP or CO.
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PMID:ATP and nitric oxide: inhibitory NANC neurotransmitters in the longitudinal muscle-myenteric plexus preparation of the rat ileum. 876 96

A microdialysis method combined with a sensitive radioimmunoassay was used to monitor cGMP release in the frontal cortex of the anesthetized rats in vivo. We assessed the relative contribution of endogenous nitric oxide (NO), and effects of exogenous carbon monoxide (CO) and phosphodiesterase activity, as possible regulators of cortical CGMP levels. Perfusion with CO-saturated aCSF (approximately 1 mM CO) failed to significantly stimulate cortical cGMP levels. For comparison, cerebellar cGMP levels increased by 2-fold during CO stimulation, followed by a prolonged response that was fully reversible with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Cortical perfusion with zinc protopophyrin-IX (100 microM), a widely used inhibitor of the CO-generating enzyme heme oxygenase, suppressed cGMP levels by 50%, a response that spontaneously recovered in spite of the continuous presence of the metalloporphyrin. Perfusion with isobutylmethyl xanthine IBMX (1 mM) resulted in 5-fold increase in cortical cGMP levels, as compared to basal levels without IBMX. In the presence of IBMX, L-NAME suppressed basal cortical cGMP levels by 70% indicating that NO synthase activity generates the bulk of cGMP in this brain region, as previously shown for basal cGMP production in the hippocampus and the cerebellum. These data also emphasize a crucial role for phosphodiesterase activity in the maintenance of cGMP levels in vivo in the frontal cortex. The relatively weak responses to exogenous CO lend little support for a role of this gas in regulating basal cortical cGMP levels in vivo.
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PMID:Regulation of cyclic GMP levels in the rat frontal cortex in vivo: effects of exogenous carbon monoxide and phosphodiesterase inhibition. 917 94

Effects of a novel zinc compound polaprezinc [N-(3-aminopropionyl)-L-histidinatozinc] and sucralfate on the mucosal ulcerogenic responses induced by monochloramine (NH2Cl) were examined in rat stomachs. Oral administration of NH2Cl (>60 mM) produced severe lesions in unanesthetized rat stomachs, with concomitant increase of lipid peroxidation. These lesions were aggravated by sensory deafferentation but not affected by pretreatment with indomethacin or L-NAME. The mucosal ulcerogenic response to NH2Cl was significantly inhibited by oral pretreatment with either dmPGE2 (10 microg/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg), the NO donor. Gastric lesions induced by NH2Cl were also inhibited by prior oral administration of polaprezinc (3-30 mg/kg) as well as sucralfate (30 and 100 mg/kg). The protective effect of polaprezinc was not affected by any pretreatments such as indomethacin, L-NAME, or sensory deafferentation, while that of sucralfate was significantly mitigated in the presence of either indomethacin or L-NAME. On the other hand, mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery, followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were also attenuated by prior application of polaprezinc, while dmPGE2 and sucralfate prevented such lesions without affecting the reduced PD response. These results suggest that: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa, (2) both polaprezinc and sucralfate protect the stomach against injury caused by NH2Cl, and (3) the mechanisms underlying the protective action of sucralfate may be partly mediated by both endogenous PGs and NO but may be different from those of polaprezinc.
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PMID:Mucosal ulcerogenic action of monochloramine in rat stomachs: effects of polaprezinc and sucralfate. 936 51

There is compelling evidence to indicate an anti-inflammatory action of Zn2+. Most inflammatory diseases are associated with an increase of the inducible form of nitric oxide (NO) synthase. Additionally, inflammatory mediators such as histamine or bradykinin stimulate the constitutive NO synthase. Thus, the present study was undertaken to investigate whether Zn2+ inhibits production of inducible NO synthase and/or constitutive NO synthase activity to produce NO. Lipopolysaccharide, 5 mg/kg i.v., administered to Zn2+-deficient (ZD) rats, rats supplemented with Zn2+ sulfate (ZG), 10 mg/kg s.c., or controls resulted in a significant reduction of their serum Zn2+. The levels of N(G)-nitro-L-arginine methylester (L-NAME)-sensitive cyclic GMP (cGMP) in aortas isolated from ZD or ZG were significantly lower than those obtained from control animals. Zinc (100-150 microM) produced a dose-dependent inhibition of lipopolysaccharide or interleukin-1beta-induced NO formation in isolated rat aortic smooth muscle cells. Compared to cyclohexamide or actinomycin-D, the time course of inhibition of NO formation by 150 microM Zn2+ did not suggest an effect of Zn2+ on inducible NO synthase protein synthesis. Moreover, Zn2+ (150 microM) significantly reduced the rate of conversion of [3H]arginine to [3H]citrulline in lung homogenates from lipopolysaccharide-treated rats. Incubation of rat aortic smooth muscle cells and bovine pulmonary artery endothelial cell co-cultures with Zn2+ (150 microM) caused a significant reduction in basal and bradykinin- or A-23187-induced formation of cGMP. Thus, our results indicate that Zn2+ is capable of inhibiting lipopolysaccharide- or interleukin-1beta-induced NO formation as well as NO formation by constitutive NO synthase basally or in response to bradykinin or A-23187, and may explain the reported anti-inflammatory activity of Zn2+.
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PMID:Zn2+ inhibits nitric oxide formation in response to lipopolysaccharides: implication in its anti-inflammatory activity. 954 48

The aim of this study was to assess the involvement in decidual proliferation of nitric oxide (NO), a regulator of many cellular processes, that is synthesized from L-arginine by NO synthase. The investigation was conducted on pseudopregnant (PG) rats in which the decidual cell reaction, the basis for the decidualization process, was surgically induced by uterine trauma on PG Day 4. Groups of animals (n = 5) were pretreated with either 2 doses/day of N(G)-nitro-L-arginine methyl ester (L-NAME) that inhibits NO synthase, or twice daily doses of L-NAME plus L-arginine combined. Drug application times coincided with 3 hr after lights on or 3 hr before lights off. The two treatment regimens (PG Days 1-4 or 5-8) respectively preceded or followed decidual induction. Animals were sacrificed at mid-light on PG Day 9, the day of maximal growth response to the deciduogenic stimulus. Parallel, time-dependent increases in both NO synthase activity and decidual growth occurred mainly in the endometrium. L-NAME produced reductions in endometrial and myometrial growth that were reversed by the combined L-NAME plus L-arginine treatments. These inhibitory effects by L-NAME were caused by only the pretraumal (PG Days 1-4) administration. Hormonally, circulating progesterone levels were similarly affected by this early treatment and may also contribute to the reduced decidual sensitivity. In contrast, serum estradiol, along with the zinc metalloenzymes, alkaline phosphatase and the matrix metalloproteinases--prominent decidualization biomarkers--were all unaffected by either the pre- or post-decidual induction dosings. The study demonstrates that inducible NO synthase/endogenous NO may physiologically participate in uterine metabolism during the decidual cell reaction. Moreover, by virtue of L-NAME inhibition of the decidual response, it appears that NO synthase/NO may influence decidual growth either by directly increasing uterine sensitivity to the deciduogenic stimulus or by indirectly affecting endometrial vascularity and subsequent availability of decidual metabolites.
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PMID:Antiproliferative effects of inducible nitric oxide synthase inhibition on decidualization in pseudopregnant rats. 957 51

Previously, we have shown that the Vibrio cholerae haemagglutinin/protease (HA/P) accounts for significant remaining toxicity of CVD110, an attenuated V. cholerae 01 El Tor live oral vaccine-strain. The present report demonstrates that endogenous nitric oxide (NO) production modulates HA/P-mediated cytotoxicity in Madin-Darby canine kidney cell strain I (MDCK-I) epithelial cells. The basal levels of endogenous NO suppressed the cytotoxicity of HA/P, whereas inhibition of NO production with nitro-L-arginine methyl-ester (L-NAME) made the MDCK-I cells susceptible even to low concentrations of the cytotoxin. The inhibition of NO production caused a reinforcement of the HA/P- mediated distortion of a tight junction-associated protein ZO-1 and increment of filamentous actin at the apical and the lateral membrane domains. The mechanism by which NO exerts its modulatory action is not likely to be from its direct interaction with the zinc-containing catalytic domain of HA/P, since two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-D, L-penicillamine (SNAP), did not affect the proteolytic activity of HA/P. In conclusion, the endogenous NO in the MDCK-I cells has a modulating effect on the cytotoxicity of HA/P and thus protects the cells against the cytotoxin.
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PMID:Endogenous nitric oxide in MDCK-I cells modulates the Vibrio cholerae haemagglutinin/protease (HA/P)-mediated cytotoxicity. 960 Aug 64

The enzyme heme oxygenase, which exists in inducible (HO-1) and constitutive (HO-2) isoforms, catalyzes the degradation of heme to biliverdin and CO in mammalian tissues. CO has been implicated in the control of vascular tone in a manner similar to that for NO. In the present study, we investigated the contribution of the heme oxygenase/CO pathway to the modulation of acute hypertensive responses in vivo induced by (1) alphaalphaHb, a chemically modified hemoglobin known to scavenge NO, and (2) NG-nitro-L-arginine methyl ester (L-NAME), a competitive NOS inhibitor. Experiments were carried out in conscious rats in which femoral arteries and veins were surgically catheterized 1 or 5 days before treatment with the vasoconstrictor agents. Intravenous infusion of alphaalphaHb (8% solution) or L-NAME (30 micromol/kg) [corrected] produced an acute and significant increase in mean arterial pressure (P<0.05) in rats at 5 days after catheter implantation. In contrast, no change in blood pressure was observed when alphaalphaHb or L-NAME was infused 1 day after the surgical intervention. The suppression of the hypertensive response observed at 1 day after surgery correlated with a significant (P<0.05) HO-1 expression in aorta, heart, and liver as well as increased aortic CO production and cGMP levels. At 1 day after surgery, pretreatment of animals with the heme oxygenase inhibitor zinc protoporphyrin IX (50 micromol/kg IP) markedly decreased aortic CO and cGMP levels and completely restored the vasoconstrictor effects of both alphaalphaHb and L-NAME. These results provide evidence for a crucial role of the heme oxygenase/CO pathway in the regulation of blood pressure under stress conditions in vivo.
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PMID:Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. 973 80

The purpose of this study was to examine the role of superoxide anions in modulating the vascular tone. The effects of unmodified and lecithinized superoxide dismutase (SOD) on vascular tone were determined in aortic ring preparations of mice. In lecithinized SOD, 4 molecules of a phosphatidylcholine derivative were covalently bound to each dimer of recombinant human copper-zinc SOD to facilitate tissue accumulation. Unmodified SOD did not change vascular tone. However, lecithinized SOD induced dose-dependent vasodilation of aortic ring preparations. The pretreatment with NG-nitro-L-arginine methylester (L-NAME) 10(-4) mol/L abolished the vasodilation induced by lecithinized SOD. The results of this study indicate that superoxide anions play a prominent role in modulating the vascular tone by enhancing the breakdown of nitric oxide.
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PMID:Lecithinized superoxide dismutase induces vasodilation; evidence of direct contribution of superoxide anions to modulating vascular tone. 1002 63

The mechanism of relaxation of the guinea-pig trachea induced by pituitary adenylate cyclase activating peptide (PACAP)-27 was investigated. We examined whether modulators of nitric oxide (NO) and carbon monoxide (CO) affect PACAP-induced response of tracheal strips in vitro. Pretreatment with N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) and L-arginine (L-arg) had no effect, while 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), haemoglobin and zinc protoporphyrin IX (ZnPP-9) partially abolished the PACAP-induced relaxation. PACAP-27 elevated cyclic GMP level in airway smooth muscle tissue. These results indicate that PACAP-27 not only induces cyclic AMP-mediated responses, but also cyclic GMP-mediated responses in the airway. In addition, CO is related to the PACAP-induced elevation of cGMP level in the tracheal tissue.
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PMID:Pituitary adenylate cyclase activating peptide induces cGMP-mediated relaxation in guinea-pig airways. 1010 45

A nitric oxide synthase (NOS) inhibitor, NG-nitro-L -arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to determine whether it prevents the intestinal damage usually observed under these conditions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg), whereas control rats including pair-fed (PF) and ad libitum consumption (AL) groups were given a zinc-supplemented (50.8 mg zinc/kg) diet for 4 wk. Half of the ZD rats received L-NAME (0.3 g/L in drinking water) for 3 wk starting at the wk 2 of the deficient period. Plasma zinc concentration in ZD rats was significantly lower (P < 0.05) than that of AL and PF rats. Administration of L-NAME did not alter this concentration. Intestinal zinc concentration did not differ among groups. However, metallothionein-1 (MT-1) mRNA level was significantly lower in the intestine of ZD rats than in AL or PF rats. Treatment of ZD rats with L-NAME did not affect this level. Intestinal microvascular permeability evaluated by Evans blue showed significantly higher extravasation in ZD rats than in AL rats, whereas L-NAME administration inhibited the extravasation. Expression of inducible NOS mRNA was observed in intestine of ZD but not of AL or PF rats, and there was no significant difference between ZD rats, regardless of L-NAME treatment. The activity ratio of inducible NOS to total NOS in ZD rats not receiving L-NAME was significantly higher than that in AL rats or ZD rats treated with L-NAME (P < 0.05). The number of apoptotic-positive and goblet cells in intestinal villi was significantly higher in ZD rats compared with AL or PF rats. L-NAME administration in ZD rats reversed this effect. These results indicate that inhibition of NOS ameliorates zinc deficiency-induced intestinal damage in rats.
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PMID:Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc deficiency in rats. 1020 52

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