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)

In order to establish whether nitric oxide (NO) is involved in the regulation of ACTH and/or GH secretion, normal male subjects were treated i.v. with the NO-synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (40 micrograms/kg injected plus 50 micrograms/kg infused over 60 min) in basal conditions and/or during stimulation with insulin (0.15 IU/kg body weight in an i.v. bolus) to induce hypoglycemia (ITT) or ASP 1 ILE-5 angiotensin II (ANG II) (increasing doses of 4, 8 and 16 ng/kg/min, each dose for 20 min). The administration of L-NAME neither changed the basal secretion of ACTH and GH nor modified the hormonal responses to ANG II stimulation. Also the GH response during ITT remained unchanged in the presence of L-NAME. In contrast, the ACTH response to hypoglycemia was significantly higher when L-NAME was administered. These data suggest that in normal men NO has a negative effect on ACTH secretion, but not GH secretion, in response to hypoglycemia. Furthermore, our results argue against a role of NO in the control of basal and ANG II-stimulated ACTH and GH secretions.
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PMID:Influence of nitric oxide on hypoglycemia--or angiotensin II-stimulated ACTH and GH secretion in normal men. 900 49

1. A constitutive nitric oxide synthase (NOSc) pathway negatively controls L-arginine-stimulated insulin release by pancreatic beta cells. We investigated the effect of glucose on this mechanism and whether it could be accounted for by nitric oxide production. 2. NOSc was inhibited by N omega-nitro-L-arginine methyl ester (L-NAME), and sodium nitroprusside (SNP) was used as a palliative NO donor to test whether the effects of L-NAME resulted from decreased NO production. 3. In the rat isolated perfused pancreas, L-NAME (5 mM) strongly potentiated L-arginine (5 mM)-induced insulin secretion at 5 mM glucose, but L-arginine and L-NAME exerted only additive effects at 8.3 mM glucose. At 11 mM glucose, L-NAME significantly inhibited L-arginine-induced insulin secretion. Similar data were obtained in rat isolated islets. 4. At high concentrations (3 and 300 microM), SNP increased the potentiation of arginine-induced insulin output by L-NAME, but not at lower concentrations (3 or 30 nM). 5. L-Arginine (5 mM) and L-ornithine (5 mM) in the presence of 5 mM glucose induced monophasic beta cell responses which were both significantly reduced by SNP at 3 nM but not at 30 nM; in contrast, the L-ornithine effect was significantly increased by SNP at 3 microM. 6. Simultaneous treatment with L-ornithine and L-arginine provoked a biphasic insulin response. 7. At 5 mM glucose, L-NAME (5 mM) did not affect the L-ornithine secretory effect, but the amino acid strongly potentiated the alteration by L-NAME of L-arginine-induced insulin secretion. 8. L-Citrulline (5 mM) significantly reduced the second phase of the insulin response to L-NAME (5 mM) + L-arginine (5 mM) and to L-NAME + L-arginine + SNP 3 microM. 9. The intermediate in NO biosynthesis, NG-hydroxy-L-arginine (150-300 microM) strongly counteracted the potentiation by L-NAME of the secretory effect of L-arginine at 5 mM glucose. 10. We conclude that the potentiation of L-arginine-induced insulin secretion resulting from the blockade of NOSc activity in the presence of a basal glucose concentration (1) is strongly modulated by higher glucose concentrations, (2) is not due to decreased NO production but (3) is probably accounted for by decreased levels of NG-hydroxy-L-arginine or L-citrulline, resulting in the attenuation of an inhibitory effect on arginase activity.
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PMID:Mechanisms involved in the effect of nitric oxide synthase inhibition on L-arginine-induced insulin secretion. 903 55

The mechanisms associated with insulin-induced cardiovascular inhibitory responses were evaluated in untreated normal rats and in normal rats pretreated with an antagonist of nitric oxide (NO) production (L-NAME), with cholinergic, alpha- and beta-adrenergic antagonists, or after ganglionic blockade. Male Wistar rats were anesthetized with a mixture of urethane and alpha-chloralose and placed on a electric heating pad. The femoral artery and vein were cannulated for measurements of mean arterial pressure (MAP), heart rate, plasma glucose, blood sampling, and intravenous injections. Intravenous injection of insulin (5.0 U/kg) in untreated rats resulted in a significant and sustained decrease in arterial blood pressure (average 24%) and in a slight decrease in heart rate. These cardiovascular responses were blocked by L-NAME and by the cholinergic antagonist atropine, suggesting an involvement of NO and the cholinergic receptors, or an effect of insulin on the central nervous system parasympathetic center. The ganglionic blocker hexamethonium attenuated the insulin-induced response. On the other hand, the hypotensive effect of insulin persisted after sympathetic blockade with the alpha-1 antagonist prazosin and the beta-1 antagonist atenolol. We conclude that the insulin-induced decrease in blood pressure is due to both increased cholinergic outflow and to NO production and that an enhanced sympathetic activity possibly mediated by a reactive release of norepinephrine or epinephrine modulates this response.
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PMID:Mechanisms mediating insulin-induced hypotension in rats. A role for nitric oxide and autonomic mediators. 903 65

1. Altered vasoreactivity may contribute significantly to the pathogenesis of diabetic vascular complications. This study investigated the effect of (a) insulin-related diabetes, and (b) chronic in vivo administration of N(omega)-nitro-L-arginine ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on mean arterial pressure and in vitro vascular reactivity to noradrenaline in mesenteric arterial bed preparations from spontaneously diabetic, insulin-dependent and treated BB rats, the best animal model of insulin-dependent mellitus (IDDM) currently available. Four groups of animals from the Edinburgh colony (BB/E) of spontaneous diabetic BB rats were studied: age-matched (mean +/- s.e. mean = 156 +/- 2d) non-diabetic (glycated haemoglobin = 3.8 +/- 0.1%) and insulin-treated diabetic (glycated haemoglobin = 6.2 +/- 0.5%; duration of diabetes = 56 +/- 4 d) groups were either L-NAME treated (oral dose = 27 +/- 1 mg kg-1 d-1; duration of treatment from 30 until 153 days of age) or untreated. Although our diabetic BB/E rats do not achieve overall normoglycaemia, individual adjustment of the daily insulin dose administered to every diabetic rat achieves better glycaemic control than previous groups studying altered vascular reactivity and endothelial dysfunction in this animal model of diabetes. 2. Mean arterial pressure (measured directly via indwelling carotid arterial cannulae) was not significantly different between non-diabetic (116 +/- 3 mmHg; n = 10) and diabetic (122 +/- 2 mmHg; n = 12) BB/E rats. L-NAME treatment significantly (P < 0.001) increased mean arterial pressure in both groups (165 +/- 6 mmHg; n = 9 and 142 +/- 4 mmHg; n = 6 respectively) but the degree of hypertension observed in L-NAME-treated diabetic rats was significantly (P < 0.01) attenuated compared to non-diabetic rats treated with L-NAME. 3. Mesenteric arterial bed preparations were cannulated under anesthesia, excised and intralumenally perfused ex vivo with noradrenaline (0.2-20 microM). Basal perfusion pressures were not significantly different in mesentery preparations from non-diabetic (27.0 +/- 2.6 mmHg) and diabetic (27.1 +/- 3.2 mmHg) BB/E rats. There was no significant difference in maximal response above basal perfusion pressure (MAX) or pEC50, defined as the negative log of the agonist concentration required to give 50% of the maximal response above basal perfusion pressure, to noradrenaline in untreated non-diabetic (166 +/- 7 mmHg and 5.74 +/- 0.05 respectively) and diabetic (170 +/- 11 mmHg and 5.59 +/- 0.05) BB/E rats. 4. In vivo treatment of non-diabetic and diabetic BB/E rats with L-NAME had no significant effect on basal perfusion pressure (25.9 +/- 4.3 mmHg and 28.5 +/- 3.9 mmHg respectively). L-NAME treatment in vivo increased (P < 0.001) MAX to noradrenaline of non-diabetic rats (224 +/- 8 mmHg) but did not affect the value for diabetic rats (178 +/- 14 mmHg). L-NAME treatment did not alter after the pEC50 values in either group (5.71 +/- 0.05 and 5.65 +/- 0.05). 5. Consistent with previous studies using vascular preparations from spontaneously diabetic BB rats, mesentery preparations from diabetic BB/E rats (n = 12) exhibited a significantly reduced vasodilator response to acetylcholine (F value = 4.4, P < 0.05) across the concentration range studied compared to non-diabetic BB/E rats (n = 12) although there was no significant difference in maximal relaxation (diabetic 53.1 +/- 4.3% vs non-diabetic 55.7 +/- 5.5%) or pEC50, (diabetic 6.92 +/- 0.25 vs non-diabetic 7.49 +/- 0.22). There was no significant (F value = 0.8, P > 0.1) difference in the response to GTN between preparations from non-diabetic and diabetic rats (maximal relaxation: 49.6 +/- 3.7% vs 48.5 +/- 4.3%; pEC50: 7.84 +/- 0.12 vs 7.89 +/- 0.22 respectively). 6. In conclusion, vascular responsiveness to noradrenaline is not impaired in spontaneously diabetic BB/E rats with significantly better glycaemic control than those used in previous studies. However, following chronic L-NAME treatment, diabetic BB/E rats exhibit attenuated hypertension and an absence of enhanced vascular responsiveness to noradrenaline in vitro compared to similarly treated non-diabetic rats. These results, together with the significantly impaired endothelium-dependent vasodilatation and unchanged endothelium-independent vasodilatation in vitro of preparations from diabetic BB/E rats, are consistent with the hypothesis that functional changes in the synthesis and metabolism of NO (rather than altered vascular responsiveness to NO) occur in diabetes. Our results indicate that good glycaemic control alone is insufficient to prevent these abnormalities in NO availability and further studies to characterize the origin of these changes are necessary.
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PMID:In vivo and in vitro evidence of altered nitric oxide metabolism in the spontaneously diabetic, insulin-dependent BB/Edinburgh rat. 911 82

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

1. We have investigated the mechanism by which L-arginine stimulates membrane depolarization, an increase of intracellular calcium ([Ca2+]i) and insulin secretion in pancreatic beta-cells. 2. L-Arginine failed to affect beta-cell metabolism, as monitored by NAD(P)H autofluorescence. 3. L-Arginine produced a dose-dependent increase in [Ca2+]i, which was dependent on membrane depolarization and extracellular calcium. 4. The cationic amino acids L-ornithine, L-lysine, L-homoarginine (which is not metabolized) and NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor) produced [Ca2+]i responses similar to that produced by L-arginine. The neutral nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NNA) and N omega-monomethyl-L-arginine (L-NAME) also increased [Ca2+]i. D-Arginine was ineffective. 5. L-Arginine did not affect whole-cell Ca2+ currents or ATP-sensitive K+ currents, but produced an inward current that was carried by the amino acid. 6. The reverse transcriptase-polymerase chain reaction demonstrated the presence of messenger RNA for the murine cationic amino acid transporters mCAT2A and mCAT2B within the beta-cell. 7. L-Arginine did not affect beta-cell exocytosis as assayed by changes in cell capacitance. 8. Our data suggest that L-arginine elevates [Ca2+]i and stimulates insulin secretion as a consequence of its electrogenic transport into the beta-cell. This uptake is mediated by the mCAT2A transporter.
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PMID:Electrogenic arginine transport mediates stimulus-secretion coupling in mouse pancreatic beta-cells. 913 Jan 59

1. To investigate the role of nitric oxide (NO) in diabetic nephropathy the effect of nitric oxide synthase (NOS) inhibition by NG-nitro-L-arginine methyl ester (L-NAME) was observed in a streptozotocin diabetic spontaneously hypertensive rat (SHR) model. 2. Two groups of SHR (n = 8) with streptozotocin-induced diabetes were studied. One group was given L-NAME 5 mg/kg bodyweight per day in the drinking water for 8 weeks while both groups received daily subcutaneous injections of Ultratard insulin. Creatinine clearance, urinary protein excretion, urinary nitrate concentration and systolic blood pressure were measured at fortnightly intervals. Rats were killed at 8 weeks and plasma angiotensin II (AngII) was measured by radioimmunoassay. 3. Renal function (endogenous creatinine clearance) remained stable in both groups. In the L-NAME group, however, there was a progressive increase in proteinuria that was highly significant at 6 weeks (22.1 +/- 2.9 compared with 6.5 +/- 0.7 mg/ 24 h per 100 g in control SHR diabetic rats P < 0.001). 4. Systolic blood pressure was significantly elevated in the L-NAME group throughout the study compared with the control group. 5. Plasma AngII was significantly elevated in the L-NAME group compared with controls (42.8 +/- 10.3 vs 15.1 +/- 1.9 pmol/L, respectively; P < 0.05). 6. Activation of the renin-angiotensin system may account, at least in part, for the resulting vasoconstrictor activity with chronic nitric oxide depletion.
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PMID:Nitric oxide synthase inhibition in a spontaneously hypertensive rat model of diabetic nephropathy. 917 57

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

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

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