scholarly journals Reactive oxygen species (ROS) from NADPH and xanthine oxidase modulate the cutaneous local heating response in healthy humans

2011 ◽  
Vol 111 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Marvin S. Medow ◽  
Natasha Bamji ◽  
Debbie Clarke ◽  
Anthony J. Ocon ◽  
Julian M. Stewart
Keyword(s):  
Reactive Oxygen Species ◽  
Blood Flow ◽  
Xanthine Oxidase ◽  
Local Heating ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ang Ii ◽  
Healthy Humans ◽  
Heat Response ◽  
Significant Attenuation

Local cutaneous heating produces vasodilation that is largely nitric oxide (NO) dependent. We showed that angiotensin II (ANG II) attenuates this by an ANG II receptor, type 1 (AT1R)-dependent mechanism that is reversible with the antioxidant ascorbate, indicating oxidative stress. Reactive oxygen species (ROS) produced by ANG II employ NADPH and xanthine oxidase pathways. To determine whether these mechanisms pertain to skin, we measured cutaneous local heating with 10 μM ANG II, using apocynin to inhibit NADPH oxidase and allopurinol to inhibit xanthine oxidase. We also inhibited superoxide with tempol, and H2O2 with ebselen. We heated the skin of the calf in 8 healthy volunteers (24.5–29.9 yr old) to 42°C and measured local blood flow to assess the percentage of maximum cutaneous vascular conductance. We remeasured while perfusing allopurinol, apocynin, ebselen, and tempol through individual microdialysis catheters. This was then repeated with ANG II combined with antioxidant drugs. tempol and apocynin alone had no effect on the heat response. Allopurinol enhanced the entire response (125% of heat alone), while ebselen suppressed the heat plateau (76% of heat alone). ANG II alone caused significant attenuation of the entire heat response (52%). When added to ANG II, Allopurinol partially reversed the ANG II attenuation. Heat with ebselen and ANG II were similar to heat and ANG II; ebselen only partially reversed the ANG II attenuation. Apocynin and tempol each partially reversed the attenuation caused by ANG II. This suggests that ROS, produced by ANG II via NADPH and xanthine oxidase pathways, modulates the response of skin to the application of heat, and thus contributes to the control of local cutaneous blood flow.

scholarly journals Role of mitochondria-derived reactive oxygen species in microvascular dysfunction in chronic kidney disease

2018 ◽  
Vol 314 (3) ◽  
pp. F423-F429 ◽  
Author(s):  
Danielle L. Kirkman ◽  
Bryce J. Muth ◽  
Meghan G. Ramick ◽  
Raymond R. Townsend ◽  
David G. Edwards
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Heating ◽  
Reactive Oxygen ◽  
Microvascular Dysfunction ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Cutaneous Vasodilation

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Mitochondrial dysfunction secondary to CKD is a potential source of oxidative stress that may impair vascular function. This study sought to determine if mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in stage 3–5 CKD. Cutaneous vasodilation in response to local heating was assessed in 20 CKD patients [60 ± 13 yr; estimated glomerular filtration rate (eGFR) 46 ± 13 ml·kg−1·1.73 m−2] and 11 matched healthy participants (58 ± 2 yr; eGFR >90 ml·kg−1·1.73 m−2). Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution, and 2) the mitochondria- specific superoxide scavenger MitoTempo. Skin blood flow was measured via laser Doppler flowmetry during standardized local heating (42°C). Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum conductance achieved with sodium nitroprusside infusion at 43°C. Urinary isofuran/F2-isoprostane ratios were assessed by gas-chromatography mass spectroscopy. Isofuran-to-F2-isoprostane ratios were increased in CKD patients (3.08 ± 0.32 vs. 1.69 ± 0.12 arbitrary units; P < 0.01) indicative of mitochondria-derived oxidative stress. Cutaneous vasodilation was impaired in CKD compared with healthy controls (87 ± 1 vs. 92 ± 1%CVCmax; P < 0.01). Infusion of MitoTempo significantly increased the plateau phase CVC in CKD patients (CKD Ringer vs. CKD MitoTempo: 87 ± 1 vs. 93 ± 1%CVCmax; P < 0.01) to similar levels observed in healthy controls ( P = 0.9). These data provide in vivo evidence that mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in CKD and suggest that mitochondrial dysfunction may be a potential therapeutic target to improve CKD-related vascular dysfunction.

Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-β1 and reactive oxygen species: a requirement for NAD(P)H oxidase

2005 ◽  
Vol 289 (2) ◽  
pp. L288-L289 ◽  
Author(s):  
Eugenia Mata-Greenwood ◽  
Albert Grobe ◽  
Sanjiv Kumar ◽  
Yelina Noskina ◽  
Stephen M. Black
Keyword(s):  
Reactive Oxygen Species ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Reactive Oxygen ◽  
Cyclic Stretch ◽  
Oxygen Species ◽  
Vegf Expression ◽  
Pulmonary Vessels ◽  
Pulmonary Arterial ◽  
Tgf Β1

Our previous studies have indicated that transforming growth factor (TGF)-β1 and VEGF expression are increased in the smooth muscle cell (SMC) layer of the pulmonary vessels of lambs with pulmonary hypertension secondary to increased pulmonary blood flow. Furthermore, we found that TGF-β1 expression increased before VEGF. Because of the increased blood flow in the shunt lambs, the SMC in the pulmonary vessels are exposed to increased levels of the mechanical force, cyclic stretch. Thus, in this study, using primary cultures of pulmonary arterial SMC isolated from pulmonary arteries of 4-wk-old lambs, we investigated the role of cyclic stretch in the apparent coordinated regulation of TGF-β1 and VEGF. Our results demonstrated that cyclic stretch induced a significant increase in VEGF expression both at the mRNA and protein levels ( P < 0.05). The increased VEGF mRNA was preceded by both an increased expression and secretion of TGF-β1 and an increase in reactive oxygen species (ROS) generation. In addition, a neutralizing antibody against TGF-β1 abolished the cyclic stretch-dependent increases in both superoxide generation and VEGF expression. Our data also demonstrated that cyclic stretch activated an NAD(P)H oxidase that was TGF-β1 dependent and that NAD(P)H oxidase inhibitors abolished the cyclic stretch-dependent increase in VEGF expression. Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-β1-dependent activation of NAD(P)H oxidase and increased generation of ROS.

scholarly journals Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase

Nanoscale ◽  
2018 ◽  
Vol 10 (25) ◽  
pp. 11820-11830 ◽  
Author(s):  
Marco Pelin ◽  
Laura Fusco ◽  
Cristina Martín ◽  
Silvio Sosa ◽  
Javier Frontiñán-Rubio ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Graphene Oxide ◽  
Xanthine Oxidase ◽  
Nadh Dehydrogenase ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Depolarization ◽  
Skin Keratinocytes

Graphene based nanomaterials induce a reactive oxygen species-mediated mitochondrial depolarization, caused by the activation of NADH dehydrogenase and xanthine oxidase.

Increased Generation of Vascular Reactive Oxygen Species by Ang II Is Mediated Via Src-Dependent Pathways in Essential Hypertension.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 685-685
Author(s):  
Rhian M Touyz ◽  
Ernesto L Schiffrin
Keyword(s):  
Reactive Oxygen Species ◽  
Essential Hypertension ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Leucine Incorporation ◽  
Oxygen Species ◽  
Ang Ii ◽  
Growth Responses ◽  
Hypertensive Patients ◽  
In Cells

42 We tested the hypothesis that augmented Ang II-induced vascular smooth muscle cell (VSMC) growth in human hypertension is mediated via Src-dependent pathways that generate reactive oxygen species (ROS). VSMCs from arteries of normotensive and hypertensive subjects were studied. Production of ROS was measured by fluorescence digital imaging using dichlorofluorescin diacetate (6 μM). The roles of Src and NADH/NADPH oxidase were assessed with the specific inhibitors, PP2 (10 μM) and diphenylene iodinium (DPI) (10 μM) respectively. c-Src phosphorylation was determined by western blot and kinase activity was assessed by measuring enolase phosphorylation. Ang II increased DCFDA fluorescence. This effect was inhibited by catalase, indicating that the signal was derived predominantly from H 2 O 2 . Ang II increased H 2 O 2 production within 40 minutes. Responses were greater (p<0.05) in cells from hypertensive patients (E max =82±nM) than normotensive subjects (E max = 67±nM). DPI and PP2, but not PP3 (inactive analogue) attenuated (p<0.05) Ang II-induced H 2 O 2 production. PP2 effects were greater in cells from hypertensive patients (delta H 2 O 2 , 28±5nM) vs controls (delta H 2 O 2 , 16±2nM). Ang II increased c-Src phosphorylation and activity, with responses 3-4 fold higher in hypertensives. DPI and PP2 (p<0.01) attenuated Ang II-induced DNA and protein synthesis, as measured by 3 H-thymidine and 3 H-leucine incorporation respectively. Growth responses in hypertensive patients were normalized by PP2. In VSMCs from hypertensive patients, Ang II-induced generation of ROS and growth are augmented. These effects are mediated, in part, by Src-dependent, NADH/NADPH oxidase-dependent cascades. Thus increased Src activity may be an upstream modulator of redox-sensitive pathways that regulate vascular growth and remodeling in essential hypertension.

scholarly journals NADPH oxidase-derived reactive oxygen species contribute to impaired cutaneous microvascular function in chronic kidney disease

2014 ◽  
Vol 306 (12) ◽  
pp. F1499-F1506 ◽  
Author(s):  
Jennifer J. DuPont ◽  
Meghan G. Ramick ◽  
William B. Farquhar ◽  
Raymond R. Townsend ◽  
David G. Edwards
Keyword(s):  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nadph Oxidase ◽  
Xanthine Oxidase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Oxidase Inhibition

Oxidative stress promotes vascular dysfunction in chronic kidney disease (CKD). We utilized the cutaneous circulation to test the hypothesis that reactive oxygen species derived from NADPH oxidase and xanthine oxidase impair nitric oxide (NO)-dependent cutaneous vasodilation in CKD. Twenty subjects, 10 stage 3 and 4 patients with CKD (61 ± 4 yr; 5 men/5 women; eGFR: 39 ± 4 ml·min−1·1.73 m−2) and 10 healthy controls (55 ± 2 yr; 4 men/6 women; eGFR: >60 ml·min−1·1.73 m−2) were instrumented with 4 intradermal microdialysis fibers for the delivery of 1) Ringer solution (Control), 2) 10 μM tempol (scavenge superoxide), 3) 100 μM apocynin (NAD(P)H oxidase inhibition), and 4) 10 μM allopurinol (xanthine oxidase inhibition). Skin blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Ng-nitro-l-arginine methyl ester (l-NAME; 10 mM) was infused to quantify the NO-dependent portion of the response. Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum CVC achieved during sodium nitroprusside infusion at 43°C. Cutaneous vasodilation was attenuated in patients with CKD (77 ± 3 vs. 88 ± 3%, P = 0.01), but augmented with tempol and apocynin (tempol: 88 ± 2 ( P = 0.03), apocynin: 91 ± 2% ( P = 0.001). The NO-dependent portion of the response was reduced in patients with CKD (41 ± 4 vs. 58 ± 2%, P = 0.04), but improved with tempol and apocynin (tempol: 58 ± 3 ( P = 0.03), apocynin: 58 ± 4% ( P = 0.03). Inhibition of xanthine oxidase did not alter cutaneous vasodilation in either group ( P > 0.05). These data suggest that NAD(P)H oxidase is a source of reactive oxygen species and contributes to microvascular dysfunction in patients with CKD.

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