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)

We examined the HCO(3)- stimulatory effects of L-NAME (N(G)-nitro-L-arginine methyl ester) in the proximal duodenum of streptozotocin (STZ)-induced diabetic rats and compared with those of 16,16-dimethyl prostaglandin E2 (dmPGE2) and vagal electrical stimulation. Male SD rats were given STZ (70 mg/kg) i.p., and the experiments were done using 1 approximately 6 week STZ-diabetic rats with blood glucose levels of >300 mg/dl. Under urethane anesthesia the HCO(3)- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. Hyperglycemic conditions appeared 1 week after STZ treatment and remained during 6 week-test period. The duodenal HCO(3)- secretory response to L-NAME was significantly decreased in STZ-diabetic rats; the degree of reduction was dependent on the duration of diabetes, and the stimulatory effect disappeared completely in rats after 5 approximately 6 weeks of diabetes. Intravenous administration of L-NAME markedly increased arterial blood pressure with significant decrease in heart rate in normal rats, whereas in STZ-diabetic rats this agent caused only pressor response without any effect on heart rate. STZ-diabetic rats also secreted significantly less amount of HCO(3)- from the duodenum in response to dmPGE2 and vagal electrical stimulation after 5 approximately 6 weeks of diabetes. These all changes observed in STZ-diabetic rats were significantly reversed by daily injection of insulin. These results suggest that 1) L-NAME failed to stimulate duodenal HCO(3)- secretion in STZ-diabetic rats, and 2) impairment of the duodenal HCO(3)- secretory ability in STZ-diabetic conditions is due to both vagal-dependent neuronal dysfunction and decreased sensitivity of the secreting cell.
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PMID:Failure of the nitric oxide synthase inhibitor to stimulate duodenal bicarbonate secretion in streptozotocin-diabetic rats. 912 71

The cardiovascular dysfunctions associated with septic shock induced by gram-negative or gram-positive bacteria (gram-positive or gram-negative septic shock) are comparable. In gram-negative septic shock, lipopolysaccharide (LPS) induces nitric oxide (NO) synthase, which contributes to the vascular hypotension and hyporeactivity to vasoconstrictors. The role of NO in gram-positive septic shock and the nature of the bacterial wall components responsible for the vascular effects of gram-positive bacteria are not well known. This study investigated the vascular effects of cell wall serotype polyosides, rhamnose glucose polymers (RGPs), from Streptococcus mutans, in comparison with lipoteichoic acid (LTA) from Staphylococcus aureus, on the induction of NO synthase activity in the rat aorta. We show that 10 microg of both RGPs and LTA per ml induced hyporeactivity to noradrenaline, L-arginine-induced relaxation, increases of 2.2- and 7.8-fold, respectively, of cyclic GMP production, and increases of 7- and 12-fold in nitrite release. All of these effects appeared after several hours of incubation and were inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Electron paramagnetic resonance spin trapping experiments demonstrated directly that RGPs and LTA induced NO overproduction (four- to eightfold, respectively) in rat aortic rings; this production was inhibited by L-NAME and prevented by dexamethasone. These results demonstrate directly the induction of NO production in vascular tissue by LTA and show that another, chemically different component of gram-positive bacteria can also have these properties. This result suggests that different components of the gram-positive bacterial wall could be implicated in the genesis of cardiovascular dysfunctions observed in gram-positive septic shock.
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PMID:Induction of nitric oxide production by polyosides from the cell walls of Streptococcus mutans OMZ 175, a gram-positive bacterium, in the rat aorta. 916 34

This study was conducted to test the hypothesis that acute, widespread N-nitro-L-arginine methyl ester (L-NAME) induced vasoconstriction and hypertension may affect glucose tolerance and insulin sensitivity in normal rats. Comparisons were made of blood pressure, intravenous glucose tolerance, and insulin response and [3H]-deoxyglucose tissue uptake between L-NAME and control treated rats. Chronically instrumented, awake rats were administered L-NAME (30 mg/kg) (n = 8) or saline (0.3 mL) (n = 8) intravenously. After blood pressure stabilized, a bolus injection containing glucose (300 mg/kg) and trace [3H]-deoxyglucose was administered. Arterial blood was sampled for evaluation of glucose tolerance, insulin response, and [3H]-deoxyglucose muscle uptake. L-NAME treated rats had a persistent 54 +/- 4 mm Hg blood pressure rise while fasting, and postload plasma glucose and insulin responses did not differ, nor did heart and striated muscle [3H]-deoxyglucose uptake differ. In conclusion, acute L-NAME induced hypertension does not result in glucose intolerance, hyperinsulinemia, or decreased [3H]-deoxyglucose muscle uptake.
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PMID:Effect of acute N-nitro-L-arginine methyl ester (L-NAME) hypertension on glucose tolerance, insulin levels, and [3H]-deoxyglucose muscle uptake. 919 16

The principal goal of the present study was to test the hypothesis that cytokines modulate glucose transport in skeletal muscle by increasing nitric oxide production. Cultured L6 skeletal muscle cells were incubated in the presence of tumour necrosis factor-alpha, interferon-gamma or lipopolysaccharide (LPS) alone or in combination for 24 h. Neither cytokines nor LPS alone induced NO production, as measured by nitrite concentrations in the medium. However, when used in combination, the two cytokines significantly stimulated NO production, and this effect was synergistically enhanced by the presence of LPS. Reverse transcriptase-PCR (RT-PCR) analysis revealed that NO release was associated with the induction of inducible (macrophage-type) NO synthase (iNOS). The increase in iNOS expression was confirmed at the protein level by Western-blot analysis and NADPH/diaphorase histochemical staining. Cytokines and LPS markedly increased basal glucose transport in L6 myocytes. Insulin also stimulated basal glucose transport, but significantly less in cells chronically exposed to cytokines/LPS. The sensitivity of L6 muscle cells to insulin-stimulated glucose transport was also significantly decreased by cytokines/LPS treatment. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) inhibited nitrite production in cytokine/LPS-treated cells, and this prevented the increase in basal glucose transport and restored muscle cell responsiveness to insulin. Cytokines/LPS exposure significantly increased GLUT1 transporter protein levels but decreased GLUT4 expression in L6 cells. l-NAME treatment prevented the increase in GLUT1 protein content but failed to restore GLUT4 transporter levels. These results demonstrate that cytokines and LPS affect glucose transport and insulin action by inducing iNOS expression and NO production in skeletal muscle cells. The data further indicate that cytokines and LPS increase the expression of the GLUT1 transporter protein by an NO-dependent mechanism.
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PMID:Cytokines modulate glucose transport in skeletal muscle by inducing the expression of inducible nitric oxide synthase. 923 Jan 32

In vivo administration of HOE 140 (a new bradykinin receptor antagonist) and L-NAME (nitric oxide synthase inhibitor) was performed in chronic streptozotocin-diabetic rats. Basal increases (in umol.g dw-1) in liver (45.0 +/- 3.4.1) and uterine (40.0 +/- 2.95) triglyceride levels in diabetic animals vs control (liver: 34.0 +/- 3.87; uterus: 30.2 +/- 4.01) were partially prevented by L-NAME (p < 0.01), HOE 140 (p < 0.01) and L-NAME + HOE 140 (p < 0.01). High glycogen levels (in mg.g dw-1) observed in diabetic uterine tissue (3.07 +/- 0.90), and decreased glycogen content detected in diabetic liver (11.64 +/- 1.50) vs. control (uterus: 1.59 +/- 0.15, liver: 17.25 +/- 0.87) were unaffected. Uterine 14CO2 production from 14C-U-Glucose (in uCi.mg dw), which is lower in diabetic (35.0 +/- 5.12) than in control (50.12 +/- 4.54) tissues, was improved by HOE 140 (p < 0.05) and L-NAME+HOE 140 (p < 0.05), while hepatic glucose oxidation was not increased by the drugs. Glycemia levels were decreased in diabetic rats injected with L-NAME and L-NAME plus HOE 140. Pancreatic 6-Keto-prostaglandin F1 alpha to Thromboxane B2 ratio was lower in diabetic animals than in controls, and L-NAME and/or HOE 140 treatment prevented the decrement. These findings suggest that vasoactive compounds might prevent streptozotocin-induced damage in pancreatic tissue from chronic diabetic rats.
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PMID:Influence of nitric oxide synthase and kinin antagonists on metabolic parameters in chronic streptozotocin-induced diabetes mellitus. 924 72

It has been suggested that there are separate insulin-stimulated and contraction-stimulated glucose transport pathways in skeletal muscle. This study examined the effects of nitric oxide on glucose transport in rat skeletal muscle by use of an isolated sarcolemmal membrane preparation and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), administered in the drinking water (1 mg/ml). Female Sprague-Dawley rats were divided into five groups: control, acute exercise, acute exercise+L-NAME, insulin stimulated, and insulin stimulated+L-NAME. Exercise (45 min of exhaustive treadmill running) increased glucose transport (37 +/- 2 to 76 +/- 5 pmol.mg-1.15 s-1) and this increase was completely inhibited by L-NAME (40 +/- 4 pmol.mg-1.15 s-1). A maximum dose of insulin increased glucose transport (87 +/- 10 pmol.mg-1.15 s-1), and adding L-NAME had no effect (87 +/- 11 pmol.mg-1.15 s-1). In addition, exercise, but not exercise+L-NAME, increased sarcolemma GLUT-4 content. This study confirms that there are separate pathways for contraction- and insulin-stimulated glucose transport. More importantly, although exercise and insulin both significantly increased glucose transport, L-NAME had no effect on insulin-stimulated glucose transport but blocked the exercise-stimulated transport. We conclude that nitric oxide is involved in the signal transduction mechanism to increase glucose transport during exercise.
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PMID:Exercise-stimulated glucose transport in skeletal muscle is nitric oxide dependent. 925

In the rat, simple carbohydrate feeding induces insulin resistance, and insulin resistance is associated with impaired endothelium dependent vasodilation. To determine if increasing insulin sensitivity corrects this defect of endothelial function, we evaluated the effects of an insulin-sensitizing agent, pioglitazone, on arterial pressure and in vitro vascular reactivity in three groups of Sprague Dawley rats: 1) control; 2) 60% fructose diet for 4 weeks; 3) 60% fructose diet plus pioglitazone (20 mg/kg daily, by oral gavage). Direct mean arterial pressure did not differ in Groups 1 (120 mm Hg +/- 2) and 2 (121 +/- 2) and was lower (P < .05) in Group 3 (112 +/- 2). In vitro uptake of tritiated glucose by adipocytes in response to insulin was reduced (P < .05) by fructose and increased (P < .01) by pioglitazone. In strips of thoracic aorta, norepinephrine-induced vasoconstriction and nitroprusside induced vasodilation did not differ among groups. However, in response to graded dose of acetylcholine, vasodilation was reduced (P < .05) by fructose; this was normalized by pioglitazone. In all groups, N(G)-nitro-L-arginine methyl ester (L-NAME) completely blocked acetylcholine-induced vasodilation. Thus, pioglitazone increased insulin sensitivity, lowered blood pressure, and normalized acetylcholine-induced vasodilation in insulin resistant, fructose-fed rats. Increasing insulin sensitivity may lower arterial pressure by augmenting endothelium dependent vasodilation.
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PMID:Increasing insulin sensitivity lowers blood pressure in the fructose-fed rat. 932 8

Significant changes in gastrointestinal function, decreased gastric secretion and motility in particular, are often observed in patients with chronic diabetes. The mechanisms leading to those remain unclear. In these studies we evaluated the gastric acid secretory response to insulin and pentagastrin in normal Wistar and streptozotocin diabetic rats. We also sought to determine the role of nitric oxide (NO) in this process. The animals were anesthetized with sodium pentobarbital. Warm saline was perfused through a polyethylene tube placed in the oesophagus and collected from the duodenum at 10 min intervals. Following a 50 min equilibration period, a bolus intra-jugular infusion of insulin (4.0 U/kg), 2-deoxyglucose (200 mg/kg) or pentagastrin 4.0 (ug/kg) was started and samples of the gastrointestinal perfusate were collected for an additional 80 min. Insulin-stimulated acid secretion peaked 60 min after bolus infusion in normal animals; a response that was significantly decreased in the diabetic rats. Similarly, 2-deoxyglucose-induced glucopenia increased gastric acid secretion to a lower extent in diabetic versus normal rats. The stimulatory response to pentagastrin was prompt and essentially equal in normal and diabetic animals. However, when hypoglycemia was prevented by glucose infusion, insulin did not stimulate gastric acid secretion in normal rats. Further, glucose infusion in these animals actually enhanced the secretory response to pentagastrin. Nitro-L-arginine methyl ester (L-NAME 20 mg/kg i.v.), an inhibitor of NO synthetase, also prevented the secretory response to insulin but not to pentagastrin. Preinfusion of arginine (100 mg/kg i.v.) in diabetic rats restored the gastric secretory response to insulin toward that of normal animals. We conclude that the gastric acid secretory response to insulin, but not to pentagastrin, is decreased in diabetic animals, that this response may operate through a NO mediated mechanism possibly set in motion by central nervous system glucopenia and that this NO-mediated mechanism is attenuated in diabetes.
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PMID:Impaired insulin but normal pentagastrin effect on gastric acid secretion in diabetic rats: a role for nitric oxide. 934 40

Advanced glycation end products (AGEs) have previously been shown to be increased in the diabetic kidney. Aminoguanidine, an inhibitor of advanced glycation, has been shown to attenuate the development of AGEs as well as the progression of renal disease in experimental diabetes. However, the precise mechanisms through which aminoguanidine acts remain to be elucidated since it is also able to act as an inhibitor of nitric oxide synthase (NOS). This study has therefore compared the effects of aminoguanidine with the effects of two other inhibitors of NOS, L-NAME and methylguanidine, on the development of experimental diabetic nephropathy. Diabetic rats were randomised to receive no treatment, aminoguanidine (1 g/l in drinking water), L-NAME (5 mg/l in drinking water) or methylguanidine (1 g/l in drinking water). Diabetic rats had increased levels of albuminuria and urinary nitrite/nitrate excretion when compared to control rats. Renal AGEs measured by fluorescence as well as by a carboxymethyllysine reactive radioimmunoassay, were elevated in diabetic rats. No changes in inducible NOS (iNOS) protein expression were detected in experimental diabetes nor did aminoguanidine affect iNOS expression. Aminoguanidine did not affect blood glucose or HbA1c but it did prevent increases in albuminuria, urinary nitrites/nitrates and renal AGE levels as measured by fluorescence and radioimmunoassay. L-NAME and methylguanidine did not retard the development of albuminuria, nor did they prevent increases in renal AGE levels, as assessed by fluorescence. However, these treatments did prevent increases in AGEs, as measured by radioimmunoassay. This study indicates that the renoprotective effect of aminoguanidine in experimental diabetes cannot be reproduced by L-NAME or methylguanidine. It is likely that the effect of aminoguanidine is mediated predominantly by decreased AGE formation rather than via NOS inhibition. It also raises the possibility that inhibition of fluorescent AGE formation may be more renoprotective than inhibition of the formation of carboxymethyllysine-containing AGEs.
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PMID:Relative contributions of advanced glycation and nitric oxide synthase inhibition to aminoguanidine-mediated renoprotection in diabetic rats. 934 94

Glucose homeostasis was studied in the spontaneously hypertensive rat (SHR). The fasting plasma glucose levels were similar in the SHR and normotensive Wistar-Kyoto (WKY) rat (102.7+/-2.4 vs. 107.4+/-4.2 mg/dl, P > 0.01). One hour after glucose challenge, the plasma glucose level was slightly but insignificantly increased in both SHR and WKY rat (117+/-2.5 vs. 114.3+/-3.2 mg/dl, P > 0.01). After N(G)nitro-L-arginine methyl ester (L-NAME) 20 mg/kg per day was administered intraperitoneally (i.p.) for 4 days, the plasma glucose level was significantly increased in the rats (SHR 167.3+/-4.9; WKY rat 136.0+/-4.8 mg/dl); the increase was significantly more pronounced in the SHR. The fasting insulin levels were similar in the SHR and WKY rats (2.3+/-0.4 vs. 2.0+/-0.3 ng/ml, P > 0.01). One hour after glucose challenge, the insulin level was significantly increased in the WKY rat (4.8+/-0.7 ng/ml) but not in the SHR (2.2+/-0.4 ng/ml). With L-NAME treatment, plasma insulin increase was noted in the WKY rat but not SHR (4.6+/-0.6 vs. 2.6+/-0.4 ng/ml, n = 8, P < 0.01). One hour after insulin 1 IU/kg was injected intramuscularly (i.m.), the plasma glucose level was significantly decreased in both the SHR (from 115.0+/-6.5 to 48.6+/-3.6 mg/dl, n = 8) and WKY rat (from 108.3+/-3.8 to 52.6+/-4.2 mg/dl, n = 8). No significant difference was noted between the decrease of the two groups (P > 0.01). The present findings suggested that NO plays a role in the glucose homeostasis of rats. NO-synthase blockade resulted in an increase of plasma glucose level. The SHR maintains normal glucose level and tolerance in spite of a defective insulin release response. This is probably due the compensatory effect of a more prominent NO-dependent glucose homeostatic function.
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PMID:The role of nitric oxide in the control of plasma glucose concentration in spontaneously hypertensive rats. 935 Aug 40

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