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)

1. The involvement of nitric oxide in the acute inhibitory effects of low doses of endotoxin, following intracerebroventricular (i.c.v.) or intravenous (i.v.) administration, on gastric acid secretion stimulated by distension or i.v. infusion of pentagastrin has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. The i.c.v. administration of E. coli endotoxin (800 ng kg-1) abolished the acid secretory response induced by gastric distension (20 cm water intragastric pressure) within 30 min of administration. 3. By contrast, submaximal rates of acid secretion induced by i.v. infusion of pentagastrin (8 micrograms kg-1 h-1) were not inhibited by i.c.v. administration of endotoxin (800 ng kg-1). 4. Prior i.c.v. administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 800 micrograms kg-1) restored the acid secretory responses to distension in rats treated with endotoxin (i.c.v.). 5. Likewise, i.v. administration of endotoxin (5 micrograms kg-1) abolished the acid secretory response induced by gastric distension within 30 min of administration. Prior i.c.v. injection of L-NAME (800 micrograms kg-1) or its i.v. administration (10 mg kg-1) restored acid secretory responses in rats receiving i.v. endotoxin. 6. The reversal by L-NAME (i.v.) of the acid inhibitory effects of endotoxin (i.v.) was prevented by L-arginine (12 mg kg-1, i.c.v. or 100 mg kg-1, i.v.), but not by its enantiomer D-arginine. 7. The present results imply the existence of an acute response to endotoxin involving NO synthesis in the brain. NO may act as a neuromodulator or neurotransmitter in a nervous reflex leading to the inhibition of acid secretion stimulated by gastric distension.
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PMID:Endotoxin inhibition of distension-stimulated gastric acid secretion in rat: mediation by NO in the central nervous system. 771 33

Impaired vascular contractility is a hallmark of sepsis and endotoxemia. The purpose of the present investigation was to determine mechanisms responsible for the abnormal contractility in sepsis using the rat cecal ligation and perforation (CLP) model. 24 h after CLP or sham surgery, rats were anesthetized with halothane and a segment of the thoracic aorta removed. Aortic rings measuring 1.6-2.0 mm in length were mounted in a water bath and stretched to optimal diameter. Aortic rings from control rats demonstrated a 57% increase in maximum contraction to phenylephrine and a 68% increase to KCl compared to aortic rings from rats with sepsis (p < .01). There was no difference in the concentrations of phenylephrine or KCl which elicited a half-maximal contraction (EC50) in control versus septic aortic rings. Removal of the endothelium increased the sensitivity of aortas to both phenylephrine and KCl in septic and control aortic rings but did not reverse the defects in contraction in sepsis. Treatment of the aortic rings with N gamma-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased contraction in aortic rings from both septic and control rats but also failed to correct the contractile defect in sepsis. The frequency and amplitude of the oscillations in wall tension which occurred with phenylephrine were slower, i.e., .07 +/- .10 vs. .17 +/- .02 Hz, for septic and control rings, respectively (p < .05), and had a greater amplitude .65 +/- .01 vs. .41 +/- .09 mN/mm, for septic and control rings, respectively (p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sepsis decreases phenylephrine- and KCl-induced aortic ring contraction and decreases the frequency of oscillations in active wall tension. 772 82

Cerebral ischemia in the gerbil results in early hippocampal changes, which include transient activation and/or translocation of protein kinase C (PKC), increased enzymatic activity of ornithine decarboxylase (ODC), and elevated DNA binding ability of activator protein-1 (AP1). The time-course of all three of these postischemic responses was found to be almost parallel, peaking at 3 hr after the ischemic insult. The effectiveness of known modulators of postischemic morphological outcome (MK-801, L-NAME, and gingkolides BN 52020 and BN 52021) in counteracting the induction of PKC, ODC, and AP1 formation was tested. These drugs were administrated as followed: MK-801 (a noncompetitive inhibitor of NMDA channel), 0.8 mg/kg i.p., 30 min before ischemia, and 5 min after the insult; L-NAME (competitive inhibitor of NO synthase), 10 mg/kg i.p., 30 min before ischemia, and 5 mg/kg, 5 min after ischemia; BN52020 and BN52021 (inhibitors of platelet-activating factor: PAF receptors) were administered as a suspension in 5% ethanol in water by oral route, 10 mg/kg for 3 days before ischemia. Three of these drugs, MK-801, L-NAME, and BN52021, significantly reduced ischemia-elevated activity of PKC and ODC, whereas AP1 formation was only partially attenuated. Our observations implicate the existence of different mechanism(s) for postischemic PKC and ODC activation, which in turn is engaged in AP1 induction.
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PMID:Modulation of ischemic signal by antagonists of N-methyl-D-aspartate, nitric oxide synthase, and platelet-activating factor in gerbil hippocampus. 774 16

Arterial vasodilation is considered to be the key factor in the development of sodium and water retention leading to ascites formation in cirrhosis. To determine if nitric oxide (NO) is involved in the pathogenesis of arterial vasodilation in cirrhosis, we measured the concentration of cyclic guanosine monophosphate (cGMP), the second messenger of NO, in arterial tissue from rats with carbon tetrachloride-induced cirrhosis. Aortic cGMP concentration was markedly increased in cirrhotic rats, particularly in those with ascites (ascites, 826 +/- 70; no ascites, 597 +/- 48; controls, 331 +/- 25 fmol/mg, ANOVA F = 23.1, P < .0001), and correlated inversely with arterial pressure (r = -.56, P < .0001) and systemic vascular resistance (r = -.69, P = .014) and directly with cardiac index (r = .74, P < .01). The chronic administration of the NO synthesis inhibitor NG-nitro-L-arginine-methyl-ester (L-NAME) (10 mg/kg/day for 7 days) induced a marked reduction in aortic cGMP concentration in cirrhotic rats with ascites to similar values obtained in L-NAME-treated control rats (86 +/- 14 vs. 89 +/- 8 fmol/mg, respectively, NS), indicating that the high-aortic cGMP content in cirrhotic rats was caused by an increased NO synthesis. Mean arterial pressure after L-NAME treatment increased to similar values in both groups of animals. These results suggest that in cirrhosis there is an increased vascular production of NO that may play a role in the pathogenesis of arterial vasodilation.
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PMID:Increased aortic cyclic guanosine monophosphate concentration in experimental cirrhosis in rats: evidence for a role of nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. 776 8

We assessed the effects of the inhibition of endogenous nitric oxide (NO) synthesis with Nw-nitro-L-arginine methyl ester (L-NAME) on water and sodium handling after NaCl load containing the inhibitor at 0, 0.5, 5 and 50 mg/kg in conscious control, hyper- and hypothyroid rats. L-NAME at 0.5 mg/kg caused a similar decrease in diuresis and natriuresis in control and hypothyroid rats, whereas no changes were seen in the hyperthyroid group. The saline load with 5 mg/kg of L-NAME produced no significant changes with respect to the 0 dose in any variable in control and hypothyroid rats, but increased natriuresis in the hyperthyroid group. The highest dose of L-NAME (50 mg/kg) increased the diuretic and natriuretic response in control and hyperthyroid groups, whereas in the hypothyroid group no urinary variable was significantly modified with respect to the 0 dose. These results indicate that the antidiuretic and antinatriuretic effects of L-NAME at low doses are suppressed in hyperthyroid rats, whereas the diuretic and natriuretic effects at high doses are absent in hypothyroid rats. Our findings suggest that the modulatory role of NO on sodium and water excretion is affected in both thyroid disorders. In addition, the highest dose of L-NAME killed hyperthyroid rats, indicating that NO plays an essential role for life in hyperthyroidism.
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PMID:Effects of Nw-nitro L-arginine methyl ester on the response to NaCl load in hyper- and hypothyroid rats. 783 23

The effect of chronic intravenous infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 8.6 mg.kg-1.day-1) on blood pressure, intrarenal blood flow distribution, and sodium and water balance was studied in conscious rats. On the 1st day of intravenous L-NAME infusion, renal medullary blood flow was reduced by 22%, renal cortical blood flow was unaltered, approximately 1 meq of sodium and 12 ml of water were retained, and blood pressure increased from 96 +/- 2 to 118 +/- 2 mmHg. Medullary blood flow was maintained at this decreased level, sodium continued to be retained, body weight continued to increase, and blood pressure remained elevated for the 5 days of L-NAME infusion. During the postcontrol period, blood flow in the renal medulla returned to levels not significantly different from control; the animals went into negative sodium balance and stopped gaining weight, and blood pressure returned to control. The present experiments indicate that decreased renal medullary blood flow and retention of sodium and water play an important role in the development of hypertension during chronic systemic L-NAME administration despite no measurable changes in renal cortical blood flow.
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PMID:Role of renal medullary blood flow in the development of L-NAME hypertension in rats. 786 23

1. The present study has evaluated the effect of iosorbide 5-mononitrate (IS-5-MN) and L-arginine on blood pressure profile during chronic administration of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 2. After a 7 day period of stabilization, normotensive male Wistar rats (n = 10) were selected and given L-NAME (50 micrograms/ml) in drinking water. Control rats (n = 10) were studied simultaneously for direct comparison of cardiovascular parameters. Blood pressure (systolic, SBP; diastolic, DBP) and heart rate were measured using a photoelectric tail cuff pulse detector; SBP and DBP were, in normotensive rats 106 +/- 2 and 78 +/- 2 mmHg (n = 10), respectively. The average water consumption per animal was about 35 ml/day resulting in a mean intake of L-NAME of about 10 mg/kg/day. 3. Twenty four hours after exposure to L-NAME, both SBP and DBP were found to be increased by 20 mm Hg; heart rate slightly decreased. During the next 13 days both SBP and DBP increased progressively reaching 170 +/- 3 and 116 +/- 3 mm Hg, respectively. 4. On day 14, six animals of either group were sacrificed and the heart, kidneys, liver, spleen, mesenteric and caudal arteries, brain stem, hypothalamus and parietal cortex were taken from determination of noradrenaline and dopamine content; blood from the renal vein was also collected and plasma concentrations of noradrenaline, adrenaline and 3,4-dihydroxyphenylethylglycol (DOPEG) determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isosorbide 5-mononitrate reverses high blood pressure in NG-nitro-L-arginine methyl ester treated rats. 789 42

The present study was designed to investigate the role of the autonomic nervous system in experimental hypertension induced by chronic administration of N-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/mL) over 6 days. L-NAME ingestion caused a large rise in resting mean arterial pressure (MAP) (175 +/- 5 mm Hg) and heart rate (HR) (440 +/- 17 beats per minute) compared to nontreated control rats (resting MAP: 112 +/- 2 mm Hg and HR: 345 +/- 8 beats per minute). Ganglionic blockade induced by trimethaphan (5 mg/kg, intravenously) caused a significantly (P < .01) greater decrease in MAP (delta -86 +/- 7 mm Hg) compared to control rats MAP (delta -44 +/- 4 mm Hg). This strongly suggests that the level of central sympathetic tone in L-NAME-treated rats is much greater than in nontreated rats. Using atenolol and atropine alone and combined, the level of resting sympathetic drive to the heart was found to be significantly increased in L-NAME-treated rats compared to control rats. However, vagal tone to the heart was found to be virtually abolished in L-NAME-treated rats compared to control rats. These results indicate that an increase in central sympathetic drive plays an important role in the hypertension induced by chronic inhibition of nitric oxide synthesis with L-NAME.
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PMID:Evidence that the autonomic nervous system plays a major role in the L-NAME-induced hypertension in conscious rats. 790 20

1. The purpose of this study was to characterize the effect of NG-nitro-L-arginine methyl ester (L-NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. 2. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. L-NAME, in concentrations up to 100 microM, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 microM, it potentiated cirazoline-induced vasoconstriction at each of the perfusion rates. 3. L-NAME but not D-NAME caused a leftward shift of cirazoline concentration-response curves with a marked increase in the maximal response. The potentiating action of L-NAME was abolished in arterial beds perfused with a Ca(2+)-free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. 4. In endothelium-intact and -denuded preparations, L-NAME potentiated KCl pressor responses; the endothelium-independent potentiation of KCl pressor activity was stereospecific, time-independent and was not prevented by the presence of dexamethasone (0.5 microM) in the perfusion medium. However, L-NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4-5 degrees C) for 2 days. 5. The absence of K+ in the perfusate did not inhibit the ability of L-NAME to potentiate alpha-adrenoceptor-mediated pressor responses, and nor did L-NAME inhibit KCl-induced vasodilatation in preconstricted arteries. It was thus concluded that L-NAME does not affect Na+/K(+)-ATPase activity. 6. No differences in the potentiating ability of L-NAME on either cirazoline- or KCl-mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats.7. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitricoxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; L-NAME causes potentiation of cirazoline- and KCl-induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats.
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PMID:The effects of perfusion rate and NG-nitro-L-arginine methyl ester on cirazoline- and KCl-induced responses in the perfused mesenteric arterial bed of rats. 791 52

Nitric oxide (NO) is a mediator of haemodynamic changes and cytotoxicity in in vivo models of inflammation such as endotoxaemic shock. The purpose of this study was to investigate whether NO may be involved in the increase of cerebral blood flow (CBF), intracranial pressure (ICP) and brain water content, known to occur in the early phase of pneumococcal meningitis. Rats injected intracisternally with live pneumococci were either untreated or received 5 mg kg-1 i.v. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Pretreatment with L-NAME prevented the increase in CBF, ICP and brain water content, as seen in untreated animals. CBF tended to return towards baseline when rats were treated with L-NAME 2 h after pneumococcal injection. Whereas none of the untreated and L-NAME-pretreated animals died during the 6 h observation period, 3 out of 9 rats treated with L-NAME and 7 out of 9 rats with simultaneous i.v. injection of L-NAME and L-arginine died. Our results provide preliminary evidence that NO may be involved as a mediator of CBF changes and oedema formation in the early phase of pneumococcal meningitis in the rat. NO inhibition, however, may have detrimental effects of still unidentified cause, as indicated by the increased mortality in treated animals. Further studies with analysis of the causes of mortality, structurally different NO synthase inhibitors and direct evaluation of NO synthase induction are needed to further support this hypothesis.
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PMID:Is nitric oxide involved as a mediator of cerebrovascular changes in the early phase of experimental pneumococcal meningitis? 791 93


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