Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nitric oxide (NO) in the regulation of gastroduodenal HCO3- secretion was investigated in anesthetized rats using the NO biosynthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME). HCO3- secretion was measured at pH 7.0 using a pH-stat method in the chambered stomach in the presence of omeprazole or in the proximal duodenum. Intravenous administration of L-NAME (1-5 mg/kg) increased HCO3- secretion in a dose-dependent manner in both the stomach and duodenum, with a concomitant elevation of arterial blood pressure. The stimulatory effect of L-NAME on HCO3- secretion was mimicked by another NO synthase inhibitor, NG-monomethyl-L-arginine (50 mg/kg), but not by the enantiomer NG-nitro-D-arginine methyl ester, and was significantly antagonized by concurrent administration of L-arginine, but not D-arginine, at 200 mg/kg. The exogenous NO donor nitroprusside (4 mg/kg) by itself decreased the rate of HCO3- secretion and significantly antagonized the HCO3- stimulatory action of L-NAME. Furthermore, the increased HCO3- secretion caused by L-NAME was significantly attenuated by prior administration of atropine (1 mg/kg, s.c.) or indomethacin (5 mg/kg, s.c.) and by bilateral vagotomy but was not influenced by sensory deafferentation after capsaicin pretreatment, though none of the treatments had any effect on the changes in blood pressure induced by L-NAME. These results suggest that L-NAME stimulates HCO3- secretion in the gastroduodenal mucosa. This action is associated with the inhibition of NO biosynthesis and may be partly dependent on vagal-cholinergic innervation and mediated by endogenous prostaglandins.
J Pharmacol Exp Ther 1993 Sep
PMID:Stimulation by nitric oxide synthase inhibitors of gastric and duodenal HCO3- secretion in rats. 769 Apr 3

1. The effects of hydrogen peroxide (H2O2, 0.1-1 mM) on the tone of the rings of rabbit aorta precontracted with phenylephrine (0.2-0.3 microM) were studied. 2. H2O2 induced a concentration-dependent relaxation of both the intact and endothelium-denuded rings. However, in the presence of intact endothelium, H2O2-induced responses were 2-3 fold larger than in its absence, demonstrating the existence of endothelium-independent and endothelium-dependent components of the vasorelaxant action of H2O2. 3. The endothelium-dependent component of H2O2-induced relaxation was prevented by NG-nitro-L-arginine methyl ester (L-NAME, 30 microM) or NG-monomethyl-L-arginine (300 microM), inhibitors of nitric oxide synthase (NOS), in a manner that was reversible by L-, but not by D-arginine (2mM). The inhibitors of NOS did not affect the responses of denuded rings. 4. Methylene blue (10 microM), an inhibitor of soluble guanylate cyclase, blocked H2O2-induced relaxation of both the intact and denuded rings. 5. H2O2 (1 mM) enhanced the efflux of cyclic GMP from both the endothelium-intact and denuded rings. The effect of H2O2 was 4 fold greater in the presence of intact endothelium and this endothelium-dependent component was abolished after the inhibition of NOS by L-NAME (30 microM). 6. In contrast to the effects of H2O2, the vasorelaxant action of stable organic peroxides, tert-butyl hydroperoxide or cumene hydroperoxide, did not have an endothelium-dependent component. Moreover, they did not potentiate the efflux of cyclic GMP from the rings of rabbit aorta. 7. Exogenous donors of NO, specifically, 3-morpholinosydnonimine (SIN-1), glyceryl trinitrate or sodium nitroprusside were used to decrease the tone of denuded rings to the level induced by endogenous NO released from intact endothelium. This procedure did not influence the vasorelaxant activity of H202, showing that H202 does not potentiate the vasorelaxant action of NO within the smooth muscle.8. Thus, H202-induced relaxation in the rabbit aorta has both endothelium-dependent and independent components. The endothelium-dependent component of the relaxant action of H202 is due to enhanced endothelial synthesis of NO.
Br J Pharmacol 1993 Sep
PMID:Involvement of nitric oxide in the endothelium-dependent relaxation induced by hydrogen peroxide in the rabbit aorta. 769 74

1. This study investigates the role of tumour necrosis factor (TNF) in the induction of nitric oxide synthase (NOS) by bacterial endotoxin (lipopolysaccharide; LPS) in a rat model of endotoxin shock. 2. In anaesthetized rats, pretreatment with a monoclonal antibody for TNF (TNFab; 20 mg kg-1, s.c., at 16 h prior to LPS) ameliorated the fall in mean arterial blood pressure (MAP) in response to LPS (2 mg kg-1, i.v.). For instance, endotoxaemia for 180 min resulted in a fall in MAP from 114 +/- 6 (control) to 84 +/- 5 mmHg (P < 0.01; n = 7). In contrast, animals pretreated with TNFab prior to LPS injection maintained significantly higher MAP when compared to LPS-control (MAP at 180 min; 118 +/- 3 mmHg; P < 0.01, n = 5). 3. Three hours of endotoxaemia was also associated with a significant reduction of the contractile effects of noradrenaline (NA) (10(-8)-10(-6) M) on the thoracic aorta ex vivo. This hyporeactivity to NA was partially restored by in vitro treatment of the vessels with NG-nitro-L-arginine methyl ester (L-NAME, 20 min, 3 x 10(-4) M). Pretreatment of rats with TNFab (20 mg kg-1; at 16 h prior to LPS) significantly (P < 0.05) attenuated the LPS-induced hyporeactivity of rat aortic rings ex vivo. L-NAME did not enhance the contractions of aortic rings obtained from TNFab pretreated LPS-rats. 4. At 180 min after LPS there was a significant elevation of the induced NOS activity in the lung (5.14 +/- 0.57 pmol citrulline mg-1 min-1, n = 8). TNFab pretreatment significantly attenuated this induction of NOS in response to LPS by 37 +/- 6% (n = 5; P<0.05).5. We conclude that the formation of endogenous TNF contributes to the induction of the calcium in dependent isoform of NOS in response to LPS in vivo. Thus, the beneficial effects of agents which inhibit either the release or the action of TNF in circulatory shock may be, in part, due to inhibition of NOS induction.
Br J Pharmacol 1993 Sep
PMID:Role of tumour necrosis factor in the induction of nitric oxide synthase in a rat model of endotoxin shock. 769 76

The intracoronary administration of bradykinin (25 ng kg-1 min-1) markedly reduces the severity of arrhythmias that occur during a 25 min occlusion of the left anterior descending coronary artery in chloralose, urethane anaesthetized dogs. This protection was abolished by the prior administration, by the same route, of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the L-arginine-nitric oxide pathway. The protective effect of bradykinin on reperfusion-induced VF was not affected by L-NAME. These results strongly suggest that the antiarrhythmic effect of bradykinin in this model is mediated by nitric oxide release. It also supports the concept that bradykinin might be a 'primary mediator' of the protective, antiarrhythmic effects of ischemic preconditioning.
Br J Pharmacol 1993 Sep
PMID:Prevention by an inhibitor of the L-arginine-nitric oxide pathway of the antiarrhythmic effects of bradykinin in anaesthetized dogs. 769 77

1. The interaction between endogenous nitric oxide (NO) and factors from the rat submandibular salivary gland such as epidermal growth factor (EGF) on gastric mucosal integrity in the rat has been investigated. 2. Bolus administration of the NO synthase inhibitor, NG nitro-L-arginine methyl ester (L-NAME; 6.25-50 mg kg-1, i.v.) to animals treated intraluminally with 0.15 N HCl resulted in a significant increase in the area of mucosal haemorrhagic damage at doses 12.5 and 50 mg kg-1. Concurrent administration of indomethacin (5 mg kg-1, i.v.) resulted in a significant haemorrhagic mucosal damage in response to L-NAME (12.5-50 mg kg-1). Administration of the highest dose of L-NAME resulted in an increase in histological damage to the rat gastric mucosa. 3. When compared to control animals, the extent of damage produced by L-NAME or L-NAME in combination with indomethacin was significantly exacerbated in rats which had been sialoadenectomized (SALX) by removal of the submandibular salivary glands. The mucosal damage in SALX rats was ameliorated by treatment with EGF (5 and 10 micrograms kg-1, i.v.). 4. L-NAME administration resulted in a small reduction of gastric mucosal blood flow as assessed by laser Doppler flowmetry (LDF). The reduction in LDF by 25 and 50 mg kg-1 L-NAME was significantly greater in SALX rats than in rats with intact salivary glands. Pretreatment of SALX rats with indomethacin did not augment this large decrease in LDF suggesting that endogenous prostanoids do not interact with NO and salivary factors in regulating mucosal microcirculation. 5. Mucosal NO biosynthesis as assessed by ['4C]-citrulline formation was reduced in SALX rats when compared to control animals. Pretreatment of SALX animals with parenterally-administered EGF(10 microg kg-1) was associated with an increase in [14C]-citrulline formation in the gastric mucosa to levels observed in control SALX rats.6. These data suggest that factors which originate from the salivary gland such as EGF interact with NO in the maintenance of mucosal integrity. The effects may be mediated at least in part by changes in gastric mucosal blood flow. Salivary glands and EGF may mediate these effects to some extent via changes in mucosal NO biosynthesis.
Br J Pharmacol 1993 Sep
PMID:Interaction of nitric oxide and salivary gland epidermal growth factor in the modulation of rat gastric mucosal integrity. 769 80

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.
Eur J Pharmacol 1993 Sep 14
PMID:Investigation of nicotine-induced relaxation of circular smooth muscle of the guinea-pig gastric fundus. 769 61

The role of nitric oxide in the mediation of (a) antidromic and (b) substance P-induced vasodilation in the pulp, lip, oral mucosa and submandibular gland was investigated in anaesthetized rats by means of laser Doppler flowmetry. Bolus or continuous infusion of N omega-nitro-L-arginine methyl ester (L-NAME) increased mean arterial blood pressure and reduced basal blood flow in the pulp but not in the lip. Electrical stimulation of the inferior alveolar nerve, in the presence of phenoxybenzamine, resulted in a long lasting vasodilation in lower lip and incisor pulp. Infusion of L-NAME enhanced the antidromic vasodilation in both lip and pulp. Pretreatment with L-arginine prevented these effects. Administration of the enantiomer (D-NAME) did not exert any effect on basal blood flow and on antidromic vasodilation. Infusion of substance P resulted in a transient vasodilation in all of the oral tissues studied. L-NAME reduced this vasodilation in the submandibular gland (only the lower doses) but it potentiated the responses in the pulp and oral mucosa. Pretreatment with L-arginine prevented the potentiated responses in the pulp and those induced by the lower doses of substance P in the oral mucosa. Thus, nitric oxide appears to differentially regulate the basal blood flow and the antidromic or substance P-induced vasodilation in the microvasculature of the lip and dental pulp.
Eur J Pharmacol 1993 Sep 14
PMID:Differential effects of nitric oxide synthesis inhibition on basal blood flow and antidromic vasodilation in rat oral tissues. 769 63

To assess the effect of endothelium-derived relaxing factor (EDRF) on the diaphragmatic microcirculation under basal conditions and after vasodilator stimulation, prepared diaphragms from anesthetized rats were studied. With bicarbonate-buffered Ringer's solution suffusing the diaphragm, the microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Drugs were applied to the surface of the diaphragm. Five series of experiments were performed. In Series 1, the effects of acetylcholine (ACh, 10(-4) M) and sodium nitroprusside (SNP, 3 x 10(-6) M) were measured before and after 15 minutes suffusion of N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). Trend analyses revealed that the vasodilator effect of SNP was not affected, while that of ACh was abolished by L-NAME. In Series 2, both ACh and SNP elicited a concentration-dependent increase in QLDF. In Series 3, following 15 minutes suffusion with L-NAME (10(-4) M), there was no change in baseline QLDF and the ACh-induced QLDF change was abolished, while the effect of SNP was maintained. In Series 4, five minutes of pretreatment with L-arginine (L-arg, 10(-2) M), followed by co-administration of L-arg (10(-2) M) and L-NAME (10(-4) M) for another 15 minutes, did not prevent the inhibitory effect on ACh-induced QLDF change by L-NAME. In Series 5, 20 minutes application of L-arg (10(-2) M) alone did not affect baseline QLDF. Also, L-arg did not influence the ACh-induced vasodilating response, whereas it slightly increased the SNP-induced vasodilating response.(ABSTRACT TRUNCATED AT 250 WORDS)
J Formos Med Assoc 1994 Sep
PMID:Differential effects of nitric oxide synthesis inhibitor on rat diaphragmatic microcirculation under basal conditions and after vasodilator stimulation. 773 9

The importance of gastrointestinal injury in endotoxin-induced shock and multiple organ failure is of great interest. In this paper we describe a method to assess the degree of intravascular congestion and bleeding into the wall of the intestine by determining the hemoglobin content of the tissue. After validating this method, we used it to study the mechanism of jejunal injury induced by intravenous injection of Escherichia coli lipopolysaccharide (LPS, 50 mg/kg bw), the role of nitric oxide release in maintaining the integrity of endothelial cells, and the participation of H2O2 production in the LPS-induced intestinal damage in rats. Our results show that after the administration of LPS at the dose of 50 mg/kg intravenously, the hemoglobin content of the jejunum (17.8 mg/100 mg tissue) increased 7.7-fold over that of control animals (2.3 mg/100 mg), reflecting a serious degree of congestion, bleeding, and damage in the gastrointestinal tract. Administration of nitro-L-arginine methyl ester (L-NAME) not only enhanced this injury, but also markedly decreased the dose of LPS necessary to induce intestinal damage. Infusion of L-arginine (300 mg/kg bolus plus infusion 600 mg/kg.h intravenously) protected the intestine against LPS or LPS plus L-NAME. Inhibition of basal nitric oxide release by L-NAME produced significant changes in cardiovascular variables, but failed to induce a significant bleeding damage. However, when inhibition of NO release was combined with enhanced H2O2 production by a small dose of LPS, a serious bleeding damage was observed. This was accompanied by a marked decrease in mesenteric blood flow and cardiac output. High dose of LPS induced the above effects, and thus could be responsible for the bleeding damage, while low dose of LPS that fails to inhibit nitric oxide, did not induce any intestinal bleeding. It seems that inhibition of NO release and stimulation of H2O2 production are both involved in the LPS-induced bleeding damage.
Shock 1994 Sep
PMID:The roles of nitric oxide and hydrogen peroxide production in lipopolysaccharide-induced intestinal damage. 774 48

The involvement of L-arginine/nitric oxide (NO) pathway in the vascular reactivity following hypovolemic hemorrhagic shock was studied in male anesthetized Wistar rats. Aortic rings from shocked rats showed a marked hyporeactivity (p < .01) to phenylephrine (PE, 1 nM to 10 microM), whereas the responsiveness to acetylcholine (ACh, 10 nM to 10 microM) remained unaffected. The response of these rings was restored to control values by N gamma-nitro-L-arginine methyl ester (L-NAME, 10 microM). D-NAME was without effect. L-Arginine (300 microM), but not D-arginine, significantly increased the vascular hyporeactivity of aortic rings from hemorrhagic shocked rats (p < .01), while it had no effect in rings from sham shocked rats. Dexamethasone (.1, 1, or 2 mg/kg), given intravenously 2 h before bleeding, significantly (p < .01) increased survival rate and reduced the severe hypotension due to hemorrhagic shock (p < .01). Additionally, aortic rings of hemorrhagic shocked rats pretreated with dexamethasone exhibited a greater contractile response to PE when compared to aortic rings from vehicle-pretreated shocked rats (p < .01). These results suggest that dexamethasone exerts beneficial effects in hemorrhagic shock by inhibiting NO synthesis.
Shock 1994 Sep
PMID:Dexamethasone prevents vascular failure mediated by nitric oxide in hemorrhagic shock. 774 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>