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

NOS activity has been recently described in airway epithelial cells. Because these cells are often ciliated we hypothesized that NO modulates airway ciliary beating. CBF was measured in cultured BBECs using video microscopy. L-NMMA, a NOS inhibitor, caused a 40% decrease in CBF following pre-stimulation with isoproterenol (8.5 +/- 0.3 Hz vs 14.6 +/- 0.2 Hz; p < 0.0001) which lasted approximately 60 minutes. Similar attenuation in CBF after isoproterenol pre-treatment was observed with another NOS inhibitor, L-NAME. NOS inhibitor-induced CBF slowing was also observed when cells were pre-stimulated with either bradykinin or substance P and was completely reversed by L-arginine or SNP but not by D-arginine. These observations demonstrate a novel NO-dependent mechanism that upregulates ciliary motility in response to stimulation.
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PMID:Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. 768 May 60

We investigated the responses of canine coronary rings to endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg). EDRF-NO-dependent relaxation to thrombin [control maximum response produced after administration of thrombin (Emax) was -85.2 +/- 7.0% of the constrictor response produced by the thromboxane analogue U-46619], acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax -80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%; Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%). Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings (-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However, neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA; 8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/- 23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was present, and the increases were no greater in LPS-treated groups than in controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of NG-substituted arginines on coronary vascular function after endotoxin. 769 Jul 46

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.
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PMID:Prevention by an inhibitor of the L-arginine-nitric oxide pathway of the antiarrhythmic effects of bradykinin in anaesthetized dogs. 769 77

1. Using isolated pulmonary resistance vessels from mature fetal lamb and chronically instrumented lambs (8-17 days old), we have examined whether hypoxic pulmonary vasoconstriction is sustained by activation of a constrictor mechanism or suppression of a dilator mechanism. 2. Hypoxia contracted both arteries and veins in vitro, and the contraction was greater with the former. After removing the endothelium, arteries responded faster to hypoxia, but the magnitude of the response remained unchanged. 3. Hypoxic arteries, unlike normally oxygenated arteries, did not contract with either indomethacin (2.8 microM) or N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). The same vessels relaxed with sodium nitroprusside (SNP, 0.001-10 microM) but not with bradykinin (0.1-100 nM). 4. Endothelin-1 (ET-1, 0.01-10 nM) contracted isolated arteries and veins under normoxic and hypoxic conditions. In both vessels, the contraction was fast in onset and subsidence, and was inhibited by the ETA receptor antagonist BQ123 (1 microM). The ET-1 precursor, big ET-1 (100 nM), also contracted arteries and veins, but compared with ET-1 its action was slower in development. Big ET-1 contraction, unlike ET-1 contraction, was curtailed by the inhibitor of the ET-1-converting enzyme, phosphoramidon (50 microM). 5. ET-1 (0.1-10 nM) had no effect on isolated arteries precontracted with a thromboxane A2 (TXA2) analogue (ONO-11113) and treated with BQ123 (10 microM). Under the same conditions, ET-1 relaxed the veins. Accordingly, in the absence of BQ123 treatment, the selective ETB receptor agonist IRL-1620 (0.1-100 nM) relaxed the contracted veins but not the arteries. 6. BQ123 (10 microM) inhibited the constriction of isolated arteries and veins to hypoxia. Likewise, in the conscious lamb a bolus of BQ123 (0.4 mg kg-1, injected into the pulmonary artery) curtailed the rise in pulmonary vascular resistance (Rpa) brought about by alveolar hypoxia without changing significantly systemic vascular resistance (Rao). Under normoxia, Rpa was insignificantly affected by BQ123. 7. The results indicate that pulmonary resistance arteries are more susceptible to hypoxia than the veins, and that hypoxic vasoconstriction does not require an intact endothelium to occur. Hypoxic tone is ascribed primarily to intramural generation of ET-1, while removal of the tonic action of a relaxant may only have an accessory role in the response.
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PMID:Involvement of endothelin-1 in hypoxic pulmonary vasoconstriction in the lamb. 771 33

Low doses of endotoxin cause vasoconstriction and hypoperfusion of the digit, small intestine, and cecum in horses. To determine the potential cause of these vascular alterations, in vitro vascular responses of palmar digital arteries and veins were determined in 8 horses after intravenous (IV) infusion of 1 L 0.9% NaCl (control) and 0.1 microgram/kg Escherichia coli 055:B5 endotoxin in 1 L of 0.9% NaCl (endotoxin-treated). Vessels were surgically removed under general anesthesia, cut into 4-mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Cumulative concentration response curves to acetylcholine, bradykinin, nitroprusside, norepinephrine, 5-hydroxytryptamine (serotonin), and endothelin were determined. Maximal relaxation or contraction and the concentrations needed to produce 50% maximal relaxation or contraction were determined. Palmar digital arteries from endotoxin-treated horses relaxed significantly less in response to acetylcholine and bradykinin (endothelium-dependent), but not to nitroprusside (endothelium-independent) when compared with arteries from control horses. Digital arteries from endotoxin-treated horses also contracted significantly more with norepinephrine but less with serotonin. Digital veins responded less than digital arteries. In another study, vascular reactivity experiments documented that acetylcholine and bradykinin were endothelium-dependent vasodilators (endothelium-denuded vessels relaxed less than control vessels) in palmar digital vessels. Additionally, maximal relaxations for both vasodilators were significantly inhibited by N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist, suggesting that acetylcholine and bradykinin cause relaxation through the nitric oxide pathway. The data from these studies indicate that low dose endotoxin impairs endothelium-dependent relaxation and augments adrenergic contraction of palmar digital arteries in horses.
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PMID:Alterations of endothelium-dependent digital vascular responses in horses given low-dose endotoxin. 777 62

1. The present study was undertaken to determine whether endothelial nitric oxide (NO) is involved in the endothelium-dependent vasodilation elicited by bradykinin (BK) in rings of newborn (1-7-day-old) piglet cerebral arteries precontracted with KCl (25 mM). 2. In these rings, BK (10(-10)-10(-6) M) induced concentration-dependent relaxation. The preincubation with the precursor of NO synthesis, L-arginine (10(-4) M), reduced KCl-induced contraction and increased the BK relaxation. However, preincubation with the NO synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME; 3 x 10(-5) M), increased KCl contraction and basal tone, and inhibited BK relaxation. 3. These results suggest that the endothelium of these arteries possesses the ability to produce NO, either basal or stimulated by agents like BK.
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PMID:Role of nitric oxide on the endothelium-dependent vasodilation in newborn piglet cerebral arteries. 783 34

1. In this study the influence of nitric oxide (NO) on the bronchoconstriction induced by bradykinin in anaesthetized and artifically ventilated guinea-pigs pretreated with atropine was investigated. 2. Aerosol administration of bradykinin (0.1-1 mM, 40 breaths) caused a dose-dependent increase in lung resistance (RL): maximum increase in RL was 2.5 fold the baseline value. Pretreatment with aerosolized NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA) (1 mM, 10 breaths every 5 min for 30 min), NO synthase inhibitors, markedly increased the bronchoconstrictor response to bradykinin. L-Arginine, but not D-arginine, (3 mM, 10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to aerosolized bradykinin caused by L-NAME and L-NMMA. 3. L-NAME (1 mM, 10 breaths every 5 min for 30 min) increased the bronchoconstriction induced by intravenous bradykinin (1-10 nmol kg-1). L-Arginine, but not D-arginine, (10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to intravenous bradykinin caused by L-NAME. 4. The increase in RL induced by capsaicin, either aerosol (10 microM, 10 breaths) or i.v. (20 nmol kg-1) was not affected by L-NAME (1 mM, 10 breaths every 5 min for 30 min). Acute resection of the vagi did not affect the bronchoconstriction evoked by bradykinin in guinea-pigs, either in the absence or presence of L-NAME (1 mM, 10 breaths every 5 min for 30 min). 4. These results suggest that, irrespective of the route of administration, bradykinin releases NO or a related molecule which exerts a bronchodilator action that opposes the bronchoconstrictor mechanisms activated by bradykinin itself.
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PMID:Evidence for reduction of bradykinin-induced bronchoconstriction in guinea-pigs by release of nitric oxide. 788 67

1. Nitric oxide (NO) has been suggested as the mediator of the vascular response to bradykinin. In the present study, we found that NO did not mediate the hypotensive response to bradykinin. In addition, the significance of kininase II in terminating a kinin-induced hypotension and the role of the adrenergic system in compensating for the acute fall in blood pressure (BP) was established. 2. In normal rats, the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) induced a rise in basal BP (delta BP = 40 +/- 6 mmHg, P < 0.0014) which was not altered by pretreatment with phentolamine (delta BP = 50 +/- 6 mmHg, NS). L-NAME did not attenuate the acute fall in BP in response to bradykinin (3-30 micrograms kg-1) or kallikrein (6-300 micrograms kg-1). However, a significant decrease was observed in the duration of the hypotensive response (P < 0.027). This shorter duration was not observed after pretreatment with phenotolamine in addition to L-NAME. Phentolamine alone prolonged the hypotensive response to bradykinin (P < 0.04). These experiments confirm the role of NO-formation as a hypotensive component in BP homeostasis but not the role of NO as a mediator in kinin-induced hypotension. It further shows that the continuous NO-release also impedes the compensatory adrenergic hypertensive response following the acute fall in BP induced by bradykinin. 3. The hypertensive response to intravenously administered phenylephrine was found to be unchanged by preadministration of L-NAME (NS) thus showing that L-NAME did not change the sensitivity to the adrenergic response. In a separate protocol on L-NAME-treated rats we found no difference in heart rate (NS) during the recovery period following bradykinin before as compared to after administration of phentolamine. It was therefore concluded that the observed alterations in the duration of the hypotensive response were most probably due to changes in peripheral vascular resistance.4. To confirm further that NO is not a mediator in kinin-induced hypotension, we used an experimental model where the response to bradykinin was prolonged by preventing kinin degradation by kininase II-converting enzyme inhibitor (CEI). To produce a hypotensive response purely dependent on kinin, the studies were performed after removal of the renin-angiotensin system by nephrectomy (Nx). In this model, bradykinin (6 microg kg-1, i.v.) induced a prolonged hypotensive response. Pretreatment with LNAME did not alter the magnitude or the progression of the hypotensive response to bradykinin, thus confirming that NO was not a mediator in BK-induced hypotension.5. To study the mechanisms involved in terminating the hypotensive response to bradykinin, the results from the Nx CEI-treated rats were compared with Nx animals not treated with CEL. In the latter group,bradykinin induced a short hypotensive response, i.e. 0.5 +/- 0.1 min as compared to the 17 +/- 1 min after CEI (P<0.003). After kininase II-inhibition (and L-NAME), BP recovery was totally dependent on the adrenergic system, since phentolamine prevented a recovery in BP during the experimental period(P<0.01, compared to the CEI/L-NAME group). These results demonstrate the importance of kininase II as the major agent in terminating a bradykinin-induced hypotension, whereas the adrenergic system plays a small, although significant role in compensating for the fall in BP. The continuous release of NO therefore not only lowers basal BP but also impedes the compensatory adrenergic response.
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PMID:The role of nitric oxide, adrenergic activation and kinin-degradation in blood pressure homeostasis following an acute kinin-induced hypotension. 788 14

We investigated the relative contribution of basal and agonist stimulated EDRF/NO release to the adjustment of coronary tone and myocardial perfusion in conscious dogs by inhibiting coronary endothelial NO formation with NG-nitro-L-arginine methyl ester (L-NAME). Chronically instrumented conscious dogs (n = 9) were prepared for measurement of mean arterial blood pressure (MAP), heart rate (HR), coronary blood flow (CF) and diameter of the left circumflex (CDLC) and left anterior descending (CDLAD) coronary artery, respectively. Intracoronary infusions of L-NAME (30.3 mM; 0.25 ml x min-1) caused significant increases in MAP and decreases in HR. CDLC decreased by 3.8% from 3.01 +/- 0.04 to 2.90 +/- 0.04 mm and CF decreases by 30% from 12.9 +/- 0.2 to 9.1 +/- 0.2 (aU). Peak reactive hyperemia (CFmax) evoked by 20-s-lasting occlusions of the left circumflex coronary artery decreased from 29.9 +/- 0.8 to 25.8 +/- 1.0 aU and maximal flow-dependent coronary dilation were reduced from 2.04 +/- 0.08 to 0.91 +/- 0.12% after inhibition of NO-synthesis. Intracoronary infusions of acetylcholine (ACh), adenosine (Ado), bradykinin (Bk), and papaverine (Pap) caused dose-dependent increases in CDLC and CF. Infusion of L-NAME nearly abolished the dilator effect of Ado on CDLC and reduced those to ACh, Bk and Pap. Increases in CF to ACh, Ado and Bk but not to Pap were reduced by L-NAME. Subsequent intracoronary infusions of L-arginine (303 mM; 0.25 ml x min-1) reduced L-NAME-induced CF-changes partly, but did not reverse coronary constriction. These results suggest that inhibition of the continuous release of nitric oxide markedly reduces myocardial perfusion in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced nitric oxide formation causes coronary vasoconstriction and impaired dilator responses to endogenous agonists and hypoxia in dogs. 791 78

We investigated the role of endogenous nitric oxide (NO) and superoxide anions in recombinant human interleukin-1 beta (rhIL-1 beta)-induced bronchial hyperresponsiveness (BHR) and neutrophilia in Brown-Norway rats. Aminoguanidine (100 mg/kg/d) administered subcutaneously for 3 d, an inhibitor of inducible NO synthase, L-arginine (100 mg/kg/d administered subcutaneously for 3 d, a specific precursor for the synthesis of NO, and apocynin (5 mg/kg/orally), an inhibitor of superoxide anion (O2-)-generating NADPH oxidase in macrophages and neutrophils, were administered prior to administration of rhIL-1 beta (500 U) intratracheally. Aminoguanidine in addition to another inhibitor of NO synthase, NW-nitro-L-arginine methyl ester (L-NAME) 100 mg kg/d administered subcutaneously for 3 d augmented bronchial responsiveness to inhaled bradykinin (BK) but not to acetylcholine (ACh), an effect reversed by L-arginine. rhIL-1 beta-treated rats also demonstrated BHR to BK but not to ACh, associated with neutrophilia in bronchoalveolar lavage fluid (BALF). rhIL-1 beta-induced BHR and neutrophilia were neither further increased by aminoguanidine nor inhibited by L-arginine. Apocynin, however, significantly inhibited rhIL-1 beta-induced BHR but not the BALF neutrophilia. Suppression of NO generation and generation of O2- from macrophages and infiltrating neutrophils may be important in rhIL-1 beta-induced airway hyperresponsiveness to bradykinin.
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PMID:Role of nitric oxide and superoxide anions in interleukin-1 beta-induced airway hyperresponsiveness to bradykinin. 792 31


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