Neuronal nitric oxide synthase-derived hydrogen peroxide effect in grafts used in human coronary bypass surgery

2017 ◽  
Vol 131 (10) ◽  
pp. 1015-1026 ◽  
Author(s):  
Patrick Wander Endlich ◽  
Rosária Dias Aires ◽  
Roberta Lins Gonçalves ◽  
Eduardo Damasceno Costa ◽  
Janaína de Paula Arantes Ângelo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Bypass Surgery ◽  
Artery Bypass ◽  
Coronary Bypass ◽  
Neuronal Nitric Oxide Synthase ◽  
Coronary Bypass Surgery ◽  
H2o2 Production ◽  
Oxide Synthase ◽  
Nnos Inhibition

Recently, H2O2 has been identified as the endothelium-dependent hyperpolarizing factor (EDHF), which mediates flow-induced dilation in human coronary arteries. Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and, besides NO, generates H2O2. The role of nNOS-derived H2O2 in human vessels is so far unknown. The present study was aimed at investigating the relevance of nNOS/H2O2 signaling in the human internal mammary artery (IMA) and saphenous vein (SV), the major conduits used in coronary artery bypass grafting. In the IMA, but not in the SV, ACh (acetylcholine)-induced vasodilatation was decreased by selective nNOS inhibition with TRIM or Inhibitor 1, and by catalase, which specifically decomposes H2O2. Superoxide dismutase (SOD), which generates H2O2 from superoxide, decreased the vasodilator effect of ACh on SV. In the IMA, SOD diminished phenylephrine-induced contraction in endothelium-containing, but not in endothelium-denuded vessels. Importantly, while exogenous H2O2 produced vasodilatation in IMA, it constricted SV. ACh increased H2O2 production in both sets of vessels. In the IMA, the increase in H2O2 was inhibited by catalase and nNOS blockade. In SV, H2O2 production was abolished by catalase and reduced by nNOS inhibition. Immunofluorescence experiments showed the presence of nNOS in the vascular endothelium and smooth muscle cells of both the IMA and SV. Together, our results clearly show that H2O2 induced endothelium-dependent vascular relaxation in the IMA, whereas, in the SV, H2O2 was a vasoconstrictor. Thus, H2O2 produced in the coronary circulation may contribute to the susceptibility to accelerated atherosclerosis and progressive failure of the SV used as autogenous graft in coronary bypass surgery.

scholarly journals Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Arjun Vivek Pendharkar ◽  
Daniel L Smerin ◽  
Lorenzo Gonzales ◽  
Eric Wang ◽  
Sabrina L Levy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Neuronal Nitric Oxide Synthase ◽  
Optogenetic Stimulation ◽  
Oxide Synthase ◽  
Nnos Expression ◽  
Stimulation Of ◽  
Nnos Inhibition

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

Role of neuronal nitric oxide synthase in mediating renal hemodynamic changes during pregnancy

2001 ◽  
Vol 281 (5) ◽  
pp. R1390-R1393 ◽  
Author(s):  
S. R. Abram ◽  
B. T. Alexander ◽  
W. A. Bennett ◽  
J. P. Granger
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Renal Plasma Flow ◽  
Neuronal Nitric Oxide Synthase ◽  
Hemodynamic Changes ◽  
Pregnant Rats ◽  
Renal Hemodynamic ◽  
Oxide Synthase ◽  
Nnos Inhibition

Renal plasma flow (RPF) and glomerular filtration rate (GFR) are markedly increased during pregnancy. We recently reported that the renal hemodynamic changes observed during pregnancy in rats are associated with enhanced renal protein expression of neuronal nitric oxide synthase (nNOS). The purpose of this study was to determine the role of nNOS in mediating renal hemodynamic changes observed during pregnancy. To achieve this goal, we examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) on kidney function in normal conscious, chronically instrumented virgin ( n = 6) and pregnant rats ( n = 9) at day 16 of gestation. Infusion of 7-NI had no effect on RPF (4.7 ± 0.7 vs. 4.8 ± 0.9 ml/min), GFR (2.2 ± 0.2 vs. 2.5 ± 0.4 ml/min), or mean arterial pressure (MAP; 127 ± 7 vs. 129 ± 10 mmHg) in virgin rats. In contrast, 7-NI infused into pregnant rats decreased RPF (8.9 ± 1.6 vs. 6.5 ± 1.4 ml/min) and GFR (4.4 ± 0.7 vs. 3.3 ± 0.7 ml/min) while having no effect on MAP (123 ± 4 vs. 123 ± 3 mmHg). In summary, inhibition of nNOS in pregnant rats at midgestation results in significant decreases in RPF and GFR. nNOS inhibition in virgin rats had no effect on renal hemodynamics. These data suggest that nNOS may play a role in mediating the renal hemodynamic changes that occur during pregnancy.

Inhibition of neuronal nitric oxide synthase by 6-nitrocatecholamines, putative reaction products of nitric oxide with catecholamines under oxidative stress conditions

2001 ◽  
Vol 356 (1) ◽  
pp. 105-110 ◽  
Author(s):  
Anna PALUMBO ◽  
Giuseppe ASTARITA ◽  
Marco d'ISCHIA
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Enzyme Activation ◽  
H2o2 Production ◽  
Reaction Products ◽  
Competitive Inhibitors ◽  
Cytochrome C Reduction ◽  
Ic50 Values ◽  
Oxide Synthase

6-Nitrodopamine and 6-nitronoradrenaline (6-nitronorepinephrine), putative products of the nitric oxide (NO)-dependent nitration of dopamine and noradrenaline, are reported to be reversible, competitive inhibitors of neuronal nitric oxide synthase (nNOS) with Ki values of 45 and 52μM respectively. The nitrocatecholamines inhibited H2O2 production in the absence of l-arginine and tetrahydrobiopterin (BH4) (the IC50 values for 6-nitrodopamine and 6-nitronoradrenaline were 85 and 55μM respectively) but without affecting cytochrome c reduction. The apparent Ki values for nitrocatecholamine inhibition of enzyme activation by BH4 were 18μM for 6-nitrodopamine and 40μM for 6-nitronoradrenaline. Both nitrocatecholamines antagonized the dimerization of nNOS induced by BH4 and by l-arginine, the effect being reversed by BH4 (more than 10μM) and l-arginine (e.g. 100μM). Overall, these results suggest that nitrocatecholamines interfere with nNOS activity by binding to the enzyme in the proximity of the substrate and BH4-binding sites near the haem group.

β-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats

2001 ◽  
Vol 280 (2) ◽  
pp. H562-H568 ◽  
Author(s):  
Roberto A. Santizo ◽  
Heidi M. Koenig ◽  
Dale A. Pelligrino
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Topical Application ◽  
Plasma Glucose ◽  
Neuronal Nitric Oxide Synthase ◽  
The Other ◽  
Neuronal Transmission ◽  
Oxide Synthase ◽  
Arteriolar Diameter ◽  
Nnos Inhibition

We examined the relative contributions from nitric oxide (NO) and catecholaminergic pathways in promoting cerebral arteriolar dilation during hypoglycemia (plasma glucose ≅ 1.4 mM). To that end, we monitored the effects of β-adrenoceptor (β-AR) blockade with propranolol (Pro, 1.5 mg/kg iv), neuronal nitric oxide synthase (nNOS) inhibition with 7-nitroindazole (7-NI, 40 mg/kg ip) or ARR-17477 (300 μM, via topical application), or combined intravenous Pro + 7-NI or ARR-17477 on pial arteriolar diameter changes in anesthetized rats subjected to insulin-induced hypoglycemia. Additional experiments, employing topically applied TTX (1 μM), addressed the possibility that the pial arteriolar response to hypoglycemia required neuronal transmission. Separately, Pro and 7-NI elicited modest but statistically insignificant 10–20% reductions in the normal ∼40% increase in arteriolar diameter accompanying hypoglycemia. However, combined Pro-7-NI was accompanied by a >80% reduction in the hypoglycemia-induced dilation. On the other hand, the combination of intravenous Pro and topical ARR-17477 did not affect the hypoglycemia response. In the presence of TTX, the pial arteriolar response to hypoglycemia was lost completely. These results suggest that 1) β-ARs and nNOS-derived NO interact in contributing to hypoglycemia-induced pial arteriolar dilation; 2) the interaction does not occur in the vicinity of the arteriole; and 3) the vasodilating signal is transmitted via a neuronal pathway.

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