Nitroxides Increase the Detectable Amount of Nitric Oxide Released from Endothelial Cells

Zöllner, Stefan; Haseloff, Reiner F.; Kirilyuk, Igor A.; Blasig, Ingolf E.; Rubanyi, Gabor M.

doi:10.1074/jbc.272.37.23076

Cited by 39 publications

(13 citation statements)

References 46 publications

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“….À under physiologic conditions to produce peroxynitrite (ONOO À ) (Zollner et al, 1997). Elevated levels of NO have previously been shown to increase BBB permeability in vitro and in vivo (Mark et al, 2004;Boje and Lakhman, 2000).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation

Lochhead

McCaffrey

Quigley

et al. 2010

J Cereb Blood Flow Metab

275

185

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The blood-brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O 2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from the TJ. Furthermore, subcellular fractionation of cerebral microvessels reveals alterations in occludin oligomeric assemblies in TJ associated with plasma membrane lipid rafts. Our data suggest that pharmacological inhibition of disease states with an HR component may help preserve BBB functional integrity.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation

Lochhead

McCaffrey

Quigley

et al. 2010

J Cereb Blood Flow Metab

275

185

View full text Add to dashboard Cite

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“…This effect was recognized as being similar to that seen after nitric oxide (NO) administration which is well known to cause vasodilatation in vivo resulting in a decrease in arterial blood pressure. The assertion that nitroxides cause hypotension via a NO related mechanism was supported by studies performed on cultured endothelial cells [92]. NO release was measured using NO chemiluminescence following Tempol administration and it was found that nitroxides increase the amount of bioavailable NO.…”

Section: Hypertensionmentioning

confidence: 97%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

460

387

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Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

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“…Thus this concentration was used for subsequent studies. DETA NONOate at 1 mM gives a steady-state concentration of NO of ϳ40 nM (10), and the steady-state release of NO from bovine aortic endothelial cells was 12.7 Ϯ 0.7 nM (41). Thus the concentration used in this study (10 Ϫ4 M) is in the range of NO released by endothelial cells.…”

Section: Methodsmentioning

confidence: 99%

Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells

Nithipatikom

Holmes

McCoy

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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surface-enhanced Raman scattering ANGIOTENSIN II (ANG II) stimulates aldosterone secretion and contraction of vascular smooth muscle (7,18,28) and contributes to the regulation of systemic blood pressure. Two ANG II receptor subtypes, AT1 and AT2, have been cloned and characterized (5, 17, 18). These receptors are seven-transmembrane G protein-coupled receptors. ANG II receptors are densely located in the adrenal cortex, particularly in zona glomerulosa (ZG) cells (12,14,33). Binding of ANG II to AT1 receptors stimulates the synthesis of aldosterone. Aldosterone is released into the circulation, acts at the kidney tubule, and enhances sodium resorption and potassium excretion (25). The absorbed sodium contributes to enhance water resorption in the kidney. This results in the increase in extracellular fluid volume and subsequent increase in arterial pressure.Inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) resulted in an increase in cellular expression of ANG II receptors in adrenal glands and smooth muscle cells (3,16,19,34,38). Administration of L-NAME to rats increased plasma aldosterone and AT1 receptor mRNA and protein in adrenal homogenates (38). Chronic administration of L-NAME to normal rats also increased cardiac AT1 and AT2 receptor expression (19). Stimulation of vascular smooth muscle cells with S-nitroso-N-acetyl-DL-penicillamine, an NO donor, significantly decreased the receptor density (B max ) but did not affect the affinity (K d ) of ANG II (3). Chronic treatment of rat vascular smooth muscle cells with NO decreased the binding of ANG II through a guanylyl cyclase/cGMP-independent mechanism. It is not known whether NO affects the expression and localization of ANG II receptors in ZG cells. We (9, 10) previously showed that acute treatment with NO inhibited the ANG II-, 25-hydroxycholesterol-, and pregnenolone-stimulated aldosterone synthesis in ZG cells, and this mechanism is guanylyl cyclase/cGMP independent. NO inhibited aldosterone biosynthesis by binding steroidogenic enzymes. The sensitivity to NO inhibition was increased at low oxygen concentrations (9). These observations led us to examine the effects of chronic exposure of ZG cells to NO on the expression of AT1 receptors and aldosterone synthesis.Adrenal endothelial cells contain NO synthase and produce NO, whereas ZG cells do not (9). Thus endothelial cells are the major source of NO in the adrenal cortex. The adrenal gland is highly vascularized, so ZG cells are in close proximity to capillaries and endothelial cells (39). Thus ZG cells are chronically exposed to endothelial NO. ANG II stimulates endothelial NO release (11). In the presence of endothelial cells, ZG cells release less aldosterone in response to ANG II compared with ZG cells alone. This reduced aldosterone release can be reversed by NO synthase inhibitors. These studies indicate that endothelial NO can regulate aldosterone release from ZG cells.In this study, the effects of chronic NO administration on the expression and localization o...

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Nitroxides Increase the Detectable Amount of Nitric Oxide Released from Endothelial Cells

Cited by 39 publications

References 46 publications

Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation

Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation

The chemistry and biology of nitroxide compounds

Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells

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