scholarly journals L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Taylor Claybaugh ◽  
Sarah Decker ◽  
Kelly McCall ◽  
Yuriy Slyvka ◽  
Jerrod Steimle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Renal Dysfunction ◽  
Cell Damage ◽  
Cyclic Guanosine Monophosphate ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Rats ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Type Ii

Rat studies demonstrated that type II diabetes mellitus (T2DM) decreases both the production and bioavailability of nitric oxide (NO). L-arginine (LA) provides the precursor for the production of NO. We hypothesized that LA dietary supplementation will preserve NO production via endothelial nitric oxide synthase (eNOS) causing renal microvascular vasodilation and increased glomerular blood flow and thus increasing glomerular filtration rate (GFR). This would impede the formation of reactive oxygen species which contributes to cell damage and death. LA supplementation preserved GFR in the treated diabetic rats compared to untreated diabetic rats. We provide evidence that this effect may be due to increased levels of eNOS and urinary cyclic guanosine monophosphate, which leads to renal microvascular vasodilation. Plasma nitrotyrosine was decreased in the LA treated rats; however, plasma nitrite levels remained unaffected as expected. Marked improvements in glucose tolerance were also observed in the LA treated diabetic rats. These results demonstrate that LA supplementation preserves NO activity and may delay the onset of insulin resistance and renal dysfunction during hyperglycemic stress. These results suggest the importance of the NO pathway in consequent renal dysfunction and in the development of insulin resistance in diabetic rats.

Increased nitric oxide production in platelets from severe chronic renal failure patients

2011 ◽  
Vol 89 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Mariana Alves de Sá Siqueira ◽  
Tatiana M.C. Brunini ◽  
Natália Rodrigues Pereira ◽  
Marcela Anjos Martins ◽  
Monique Bandeira Moss ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Dialysis Treatment ◽  
Cgmp Pathway

Nitric oxide (NO) production occurs through oxidation of the amino acid l-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated ( da Silva et al. 2005 ) an enhancement of the l-arginine–NO–cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet l-arginine–NO–cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

scholarly journals Muscle fiber type differences in nitrate and nitrite storage and nitric oxide signaling in rats

2020 ◽  
Author(s):  
Gary M. Long ◽  
Derrick A. Gray ◽  
Ashley D. Troutman ◽  
Amanda Fisher ◽  
Mary Beth Brown ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cgmp Level ◽  
No Production ◽  
Nitric Oxide Signaling ◽  
Slow Twitch ◽  
Fast Twitch

AbstractRecent studies have emphasized the importance of the nitric oxide synthase (NOS)-independent, nitrate (NO3−) → nitrite (NO2−) → nitric oxide (NO) pathway in skeletal muscle. In particular, it has been hypothesized that this pathway is especially active in type II, or fast-twitch, muscle fibers, necessitating greater NO3− and NO2− storage. We therefore measured NO3− and NO2− concentrations in the predominantly fast-twitch vastus lateralis and predominantly slow-twitch soleus muscles of rats. Contrary to the above hypothesis, we found that NO3− and NO2− concentrations were 3.4-fold and 1.8-fold higher, respectively, in the soleus. On the other hand, NO signaling (i.e., cyclic guanosine monophosphate (cGMP) level) was comparable in the two muscles. Although the physiological significance of these observations remains to be determined, we speculate that NO production via the NO3− → NO2− → NO pathway is normally higher in slow-twitch muscles, thus helping compensate for their inherently lower NOS activity.

scholarly journals Lespedeza davurica(Lax.) Schindl. Extract Protects against Cytokine-Inducedβ-Cell Damage and Streptozotocin-Induced Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Bhesh Raj Sharma ◽  
Dong Young Rhyu
Keyword(s):  
Nitric Oxide ◽  
Blood Glucose ◽  
Cell Damage ◽  
Oral Treatment ◽  
Urine Volume ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
No Production ◽  
Protective Effects ◽  
Lespedeza Davurica

Lespedezahas been used for the management of diabetes in folklore medicine. The purpose of this study is to investigate the protective effects of the methanol extract ofLespedeza davurica(LD) on cytokine-inducedβ-cell damage and streptozotocin- (STZ-) induced diabetes. RINm5F cells were treated with interleukin- (IL-) 1βand interferon- (IFN-)γto induce pancreaticβ-cell damage. The exposure of LD extract significantly decreased cell death, nitric oxide (NO) production, nitric oxide synthase (iNOS) expression, and nucleus factor-kappa B (NF-κB) p65 activation. Antidiabetic effects of LD extract were observed by oral glucose tolerance test (OGTT) in normal rats and by checking the biochemical, physiological, and histopathological parameters in STZ-induced diabetic rats. In OGTT, glucose clearance levels improved by oral treatment of LD extract. The water intake, urine volume, blood glucose, and serum TG, TC, TBARS, and DPP-IV levels were significantly decreased, and liver glycogen content was significantly increased by treatment of LD extract (250 mg/kg BW) in STZ-induced diabetic rats. Also, insulin immunoreactivity of the pancreases was increased in LD extract administrated rats compared with diabetic control rats. These results indicate that LD extract may protect pancreaticβ-cell damage and regulate the blood glucose in STZ-induced diabetic rats.

scholarly journals Calcium blood level modulates endogenous nitric oxide action: effects of parathroidectomy in patients with hyperparathyroidism

1998 ◽  
Vol 156 (2) ◽  
pp. 231-235 ◽  
Author(s):  
V Martina ◽  
GA Bruno ◽  
V Brancaleoni ◽  
E Zumpano ◽  
M Tagliabue ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Normal Values ◽  
Normal Subjects ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Blood Levels ◽  
Free Calcium ◽  
No Production ◽  
High Calcium

Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the activity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn, is activated by a calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in platelet free calcium levels is present. In this study we evaluate the platelet cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1-methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by H-PTH before and after removal of adenoma. Platelet cGMP levels were also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P < 0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH was also correlated with t-Ca (P < 0.001), rs = 0.840). In conclusion: (1) levels of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that the increase in NO production could be a mechanism to downregulate the vasoconstriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calcium levels, NO production also returned to normal values.

scholarly journals Nitric Oxide Suppresses the Expression of Bcl-2 Binding Protein BNIP3 in Hepatocytes

2001 ◽  
Vol 276 (50) ◽  
pp. 46887-46895 ◽  
Author(s):  
Ruben Zamora ◽  
Louis Alarcon ◽  
Yoram Vodovotz ◽  
Binnie Betten ◽  
Peter K. M. Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cultured Cells ◽  
Binding Protein ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Northern Analysis ◽  
No Production ◽  
No Donor ◽  
Factor Α

Nitric oxide (NO) is not only an important signaling molecule, but it also regulates the expression of a number of genes in the liver. We have previously shown that apoptosis in hepatocytes exposed to tumor necrosis factor-α and actinomycin D is prevented by NO derived from the inducible nitric-oxide synthase (iNOS), by mechanisms that are both dependent on and independent of modulation of cyclic guanosine monophosphate (cGMP) subsequent to activation of soluble guanylyl cyclase (sGC). We hypothesize that one mechanism by which NO exerts these effects is by regulating the expression of genes involved in apoptosis. We used differential display-polymerase chain reaction to isolate NO-regulated genes in hepatocytes fromiNOSknockout mice (to eliminate endogenous inducible NO production). Using this analysis, we identified a NO-suppressed gene fragment homologous with the pro-apoptotic Bcl-2 binding protein BNIP3. Northern analysis confirmed the NO-dependent suppression ofBNIP3in cultured cells. Similarly, the NO donorS-nitroso-N-acetyl-dl-penicillamine (1–1000 μm) down-regulated the expression ofBNIP3in bothiNOSknockout and wild-type hepatocytes. This effect of NO was reversed by the sGC inhibitor 1H-(1,2,4)-oxadiazole[4,3-a]quinoxalon-1-one (ODQ),suggesting the involvement of the sGC/cGMP pathway in the modulation of BNIP3 by NO. We propose that suppression of BNIP3 expression is one sGC/cGMP-dependent mechanism by which NO might affect the process of hepatocyte apoptosis.

scholarly journals THE ADMINISTRATION OF FISH OIL TO PREGNANT RATS AGAINST THE BACKGROUND OF STRESS PREVENTS THE DISORDERS OF NITRIC OXIDE FORMATION AND ACTION IN OFFSPRING

2021 ◽  
Vol 20 (4) ◽  
pp. 27-37
Author(s):  
A.N. Pauliukevich ◽  
Keyword(s):  
Nitric Oxide ◽  
Fish Oil ◽  
Blood Serum ◽  
Cyclic Guanosine Monophosphate ◽  
Female Offspring ◽  
Guanosine Monophosphate ◽  
Control Fish ◽  
No Production ◽  
Diene Conjugates ◽  
Pregnant Rats

Objectives. To assess the possibility to prevent the disturbances of nitric oxide (NO) formation and action system in prenatally stressed rats with the help of fish oil administered to their mothers during pregnancy against the background of stress. Material and methods. Outbred pregnant rats weighing 180-220 g were divided into equal groups (n=10): «Pregnant control», «Pregnant stress», «Pregnant control + fish oil», «Pregnant stress+fish oil». Stress was reproduced by exposure to stressors on different days of pregnancy: food deprivation during one day, contact with cats’ feces during one day, and immobilization in water (20 minutes, t°=23±2). Rats of the groups «Pregnant control + fish oil» and «Pregnant stress + fish oil» received 0.1 ml of fish oil (Biosola, Lithuania) as a gavage at a daily dose of 60 mg/kg of eicosapentaenoic and docosahexaenoic acids; rats of groups «Pregnant control» and «Pregnant stress» received an equivalent volume of starch solution (0.1 ml). In 3-month-old offspring (n=181), systolic, diastolic, and mean arterial pressure (SBP, DBP, MAP, respectively) were measured noninvasively; the concentration of endothelial and inducible isoforms of NO-synthase (eNOS and iNOS, respectively), cyclic guanosine monophosphate (cGMP), asymmetric dimethylarginine (ADMA) was determined in blood serum by ELISA; the content of nitrates/nitrites (NO<sub>3</sub><sup>-</sup>/NO<sub>2</sub><sup>-</sup>), diene conjugates (DC), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase was determined spectrophotometrically in blood serum. Results. Fish oil which was administered to pregnant rats under stress led to the increase of reduced compared with control males content of eNOS, cGMP, SOD, catalase, NO<sub>3</sub><sup>-</sup>/NO<sub>2</sub><sup>-</sup> (by 10.7%, 48.3%, 62.6%, 31.3%, 91.7%, respectively); the decrease of increased concentration of iNOS, ADMA, DC, MDA (by 21.8%, 37.4%, 61.2%, 75.9%, respectively) in the blood serum of male offspring. In female offspring of group «Pregnant stress + fish oil» the decrease of increased content of iNOS, DC, MDA (by 25.8%, 2.6 and 4.9 times, respectively) with the increase of reduced concentration of NO<sub>3</sub><sup>-</sup>/NO<sub>2</sub><sup>-</sup>, SOD (by 84.6%, 52%, respectively) were determined in the blood serum. The introduction of fish oil to pregnant rats against the background of stress prevented SBP, DBP, and MAP increasing in the offspring. Conclusions. The administration of fish oil to rats during pregnancy under chronic stress prevents the impairment of NO production and action in the offspring.

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