scholarly journals Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1097
Author(s):  
Joanna M Wierońska ◽  
Paulina Cieślik ◽  
Leszek Kalinowski
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Hypoxia Inducible Factor ◽  
Inflammatory Cells ◽  
Reactive Astrocytes ◽  
Ischemic Hypoxia ◽  
Inflammatory Proteins ◽  
Brain Tissue Damage

Brain ischemia is one of the leading causes of disability and mortality worldwide. Nitric oxide (NO•), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal and glial activity constitutes the crucial factor that contributes to the development of pathological changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood flow is the massive production of reactive oxygen and nitrogen species (ROS/RNS) in neurons due to NO• synthase uncoupling, which leads to neurotoxicity. Progression of apoptotic or necrotic neuronal damage activates reactive astrocytes and attracts microglia or lymphocytes to migrate to place of inflammation. Those inflammatory cells start to produce large amounts of inflammatory proteins, including pathological, inducible form of NOS (iNOS), which generates nitrosative stress that further contributes to brain tissue damage, forming vicious circle of detrimental processes in the late stage of ischemia. S-nitrosylation, hypoxia-inducible factor 1α (HIF-1α) and HIF-1α-dependent genes activated in reactive astrocytes play essential roles in this process. The review summarizes the roles of NO•-dependent pathways in the early and late aftermath of stroke and treatments based on the stimulation or inhibition of particular NO• synthases and the stabilization of HIF-1α activity.

scholarly journals Oxidative and nitrosative stress in brain mitochondria of diabetic rats

2005 ◽  
Vol 187 (1) ◽  
pp. 37-44 ◽  
Author(s):  
R Mastrocola ◽  
F Restivo ◽  
I Vercellinatto ◽  
O Danni ◽  
E Brignardello ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Manganese Superoxide Dismutase ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Brain Mitochondria ◽  
Brain Dysfunction ◽  
Diabetic Rats ◽  
Oxidative And Nitrosative Stress ◽  
Chronic Hyperglycemia ◽  
Mitochondrial Nitric Oxide Synthase

Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.

HIF-1 expression in healing wounds: HIF-1α induction in primary inflammatory cells by TNF-α

2001 ◽  
Vol 281 (6) ◽  
pp. C1971-C1977 ◽  
Author(s):  
Jorge E. Albina ◽  
Balduino Mastrofrancesco ◽  
Joseph A. Vessella ◽  
Claudine A. Louis ◽  
William L. Henry ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Inflammatory Cells ◽  
Raw 264.7 Cells ◽  
Vascular Endothelial ◽  
Oxygen Intermediates ◽  
Tnf Α ◽  
Endothelial Growth Factor

The expression of the hypoxia-responsive transcription factor hypoxia-inducible factor (HIF)-1 during acute inflammation was investigated in experimental wounds. HIF-1α mRNA was maximally expressed in wound cells 6 h after injury. HIF-1α protein was detectable in wound cells 1 and 5 days after injury. Cells from 1-day-old wounds were not hypoxic, as determined by lack of pimonidazole hydrochloride adduct formation. Tumor necrosis factor (TNF)-α, but not interleukin-1β, increased the HIF-1α protein content of cells isolated 1 and 5 days after injury, and also of glycogen-elicited peritoneal cells, but not HIF-1α mRNA. HIF-1α did not accumulate in TNF-α-treated HeLa, NIH/3T3, NR8383, or RAW 264.7 cells. Nitric oxide from S-nitrosoglutathione did not induce HIF-1α accumulation or modulate the response to TNF-α. TNF-α did not increase oxygen consumption or result in the production of reactive oxygen intermediates by day 1 wound cells. Vascular endothelial growth factor mRNA in wound cells peaked 24 h after wounding. HIF-1 expression in early wounds may contribute to the regulation of inducible nitric oxide synthase and vascular endothelial growth factor, two HIF-1-responsive genes intimately related to the process of repair.

scholarly journals Cerebral Microvascular Damage Occurs Early after Hypoxia–Ischemia via nNOS Activation in the Neonatal Brain

2014 ◽  
Vol 34 (4) ◽  
pp. 668-676 ◽  
Author(s):  
Yi-Ching Hsu ◽  
Ying-Chao Chang ◽  
Yung-Chieh Lin ◽  
Chun-I Sze ◽  
Chao-Ching Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Damage ◽  
Cerebral Perfusion ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Nitric Oxide Synthases ◽  
Neonatal Brain ◽  
Microvascular Damage ◽  
Vascular Lumen

Microvascular injury early after hypoxic ischemia (HI) may contribute to neonatal brain damage. N-methyl-D-aspartate receptor overstimulation activates neuronal nitric oxide synthases (nNOS). We hypothesized that microvascular damage occurs early post-HI via nNOS activation and contributes to brain injury. Postpartum day-7 rat pups were treated with 7-nitroindazole (7-NI) or aminoguanidine (AG) before or after HI. Electron microscopy was performed to measure neuronal and endothelial cell damage. There were vascular lumen narrowing at 1 hour, pyknotic neurons at 3 hours, and extensive neuronal damage and loss of vessels at 24 hours post HI. Early after reoxygenation, there were neurons with heterochromatic chromatin and endothelial cells with enlarged nuclei occluding the lumen. There was also increased 3-nitrotyrosin in the microvessels and decreased cerebral blood perfusion. 7-NI and AG treatment before hypoxia provided complete and partial neuroprotection, respectively. Early post-reoxygenation, the AG group showed significantly increased microvascular nitrosative stress, microvascular interruptions, swollen nuclei that narrowed the vascular lumen, and decreased cerebral perfusion. The 7-NI group showed significantly decreased microvascular nitrosative stress, patent vascular lumen, and increased cerebral perfusion. Our results indicate that microvascular damage occurs early and progressively post HI. Neuronal nitric oxide synthases activation contributes to microvascular damage and decreased cerebral perfusion early after reoxygenation and worsens brain damage.

1618: Real-Time Monitoring of Nitric Oxide and Blood Flow During Ischemia-Reperfusion in the Rat Testis

2006 ◽  
Vol 175 (4S) ◽  
pp. 521-521
Author(s):  
Motoaki Saito ◽  
Tomoharu Kono ◽  
Yukako Kinoshita ◽  
Itaru Satoh ◽  
Keisuke Satoh
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Real Time ◽  
Ischemia Reperfusion ◽  
Real Time Monitoring ◽  
Rat Testis

Role of Nitric Oxide on Papillary Blood Flow and Pressure Natriuresis

Hypertension ◽  
1995 ◽  
Vol 25 (3) ◽  
pp. 408-414 ◽  
Author(s):  
Francisco J. Fenoy ◽  
Paloma Ferrer ◽  
Luis Carbonell ◽  
Miguel García-Salom
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pressure Natriuresis

Interactions Between Nitric Oxide and Angiotensin II on Renal Cortical and Papillary Blood Flow

Hypertension ◽  
1997 ◽  
Vol 30 (5) ◽  
pp. 1175-1182 ◽  
Author(s):  
María Isabel Madrid ◽  
Miguel García-Salom ◽  
Jerónimo Tornel ◽  
Marc de Gasparo ◽  
Francisco J. Fenoy
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii

Nitric oxide release in rat skeletal muscle capillary

1996 ◽  
Vol 270 (5) ◽  
pp. H1696-H1703 ◽  
Author(s):  
D. Mitchell ◽  
K. Tyml
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Leukocyte Adhesion ◽  
Microvascular Blood Flow ◽  
Capillary Length ◽  
Nitric Oxide Release ◽  
Longus Muscle ◽  
Potent Vasodilator ◽  
Capillary Bed ◽  
Synthase Inhibitor

Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 micron(s) from the feeding arteriole) reduced red blood cell (RBC) velocity [VRBC; control VRBC = 238 +/- 58 (SE) micron/s; delta VRBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (Dcon = 6.3 +/- 0.7 micron, delta D = 5 +/- 7%) or draining venule diameter (Dcon = 10.1 +/- 0.6 micron, delta D = 4 +/- 2%). Because of the VRBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 micron capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 micron. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary VRBC. Bradykinin (BK) locally applied to the capillary caused significant increases in VRBC (delta VRBC = 111 +/- 23%) and in arteriolar diameter (delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (delta VRBC = -4 +/- 27%; delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.

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