Endothelium-derived reactive oxygen species and endothelin-1 attenuate NO-dependent pulmonary vasodilation following chronic hypoxia

2004 ◽  
Vol 287 (4) ◽  
pp. L801-L808 ◽  
Author(s):  
Nikki L. Jernigan ◽  
Benjimen R. Walker ◽  
Thomas C. Resta
Keyword(s):  
Reactive Oxygen Species ◽  
Receptor Antagonist ◽  
Chronic Hypoxia ◽  
Reactive Oxygen ◽  
Inhibitory Influence ◽  
Oxygen Species ◽  
No Donor ◽  
Endothelin 1 ◽  
Pulmonary Vasodilation ◽  
Spermine Nonoate

Vasodilatory responses to exogenous nitric oxide (NO) are diminished following exposure to chronic hypoxia (CH) in isolated, perfused rat lungs. We hypothesized that both endothelium-derived reactive oxygen species (ROS) and endothelin-1 (ET-1) mediate this attenuated NO-dependent pulmonary vasodilation following CH. To test this hypothesis, we examined vasodilatory and vascular smooth muscle (VSM) Ca2+ responses to the NO donor spermine NONOate in UTP-constricted, isolated pressurized small pulmonary arteries from control and CH rats. Consistent with our previous findings in perfused lungs, we observed attenuated NO-dependent vasodilation following CH in endothelium-intact vessels. However, in endothelium-denuded vessels, responses to spermine NONOate were augmented in CH rats compared with controls, thus demonstrating an inhibitory influence of the endothelium on NO-dependent reactivity following CH. Whereas both the ROS scavenger tiron and the ETA receptor antagonist BQ-123 augmented NO-dependent reactivity in endothelium-intact vessels from CH rats, neither fully restored vasodilatory responses to those observed following endothelium denudation in vessels from CH rats. In contrast, the combination of tiron and BQ-123 or the nonselective ET receptor antagonist PD-145065 enhanced NO responsiveness in endothelium-intact vessels from CH rats similar to that observed following endothelium denudation. We conclude that both endothelium-derived ROS and ET-1 attenuate NO-dependent pulmonary vasodilation following CH. Furthermore, CH augments pulmonary VSM reactivity to NO.

scholarly journals Interaction between reactive oxygen species and nitric oxide in the microvascular response to systemic hypoxia

2002 ◽  
Vol 93 (4) ◽  
pp. 1411-1418 ◽  
Author(s):  
Dawn R. S. Steiner ◽  
Norberto C. Gonzalez ◽  
John G. Wood
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Leukocyte Adherence ◽  
No Donor ◽  
Substrate Limitation ◽  
Systemic Hypoxia ◽  
Microvascular Response ◽  
Spermine Nonoate

Systemic hypoxia results in oxidative stress due to a change in the reactive oxygen species (ROS)-nitric oxide (NO) balance. These experiments explored two mechanisms for the altered ROS-NO balance: 1) decreased NO synthesis by NO synthase due to limited O2 substrate availability and 2) increased superoxide generation. ROS levels and leukocyte adherence in mesenteric venules of rats during hypoxia were studied in the absence and presence of an NO donor [spermine NONOate (SNO)] and of the NO precursorl-arginine. We hypothesized that if the lower NO levels during hypoxia were due to O2 substrate limitation,l-arginine would not prevent hypoxia-induced microvascular responses. Graded hypoxia (produced by breathing 15, 10, and 7.5% O2) increased both ROS (123 ± 6, 148 ± 11, and 167 ± 3% of control) and leukocyte adherence. ROS levels during breathing of 10 and 7.5% O2 were significantly attenuated by SNO (105 ± 6 and 108 ± 3%, respectively) andl-arginine (117 ± 5 and 115 ± 2%, respectively). Both interventions reduced leukocyte adherence by similar degrees. The fact that the effects of l-arginine were similar to those of SNO does not support the idea that NO generation is impaired in hypoxia and suggests that tissue NO levels are depleted by the increased ROS during hypoxia.

The positive inotropic effect of endothelin-1 is mediated by mitochondrial reactive oxygen species

Life Sciences ◽  
2008 ◽  
Vol 83 (7-8) ◽  
pp. 264-271 ◽  
Author(s):  
V.C. De Giusti ◽  
M.V. Correa ◽  
M.C. Villa-Abrille ◽  
C. Beltrano ◽  
A.M. Yeves ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Positive Inotropic Effect ◽  
Reactive Oxygen ◽  
Inotropic Effect ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Endothelin 1

Endothelin-1 Induces Cyclooxygenase-2 Expression and Generation of Reactive Oxygen Species in Endothelial Cells

2004 ◽  
Vol 44 (Supplement 1) ◽  
pp. S332-S335 ◽  
Author(s):  
Toru Sugiyama ◽  
Takanobu Yoshimoto ◽  
Ryuji Sato ◽  
Nozomi Fukai ◽  
Naoko Ozawa ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Reactive Oxygen ◽  
Cyclooxygenase 2 ◽  
Oxygen Species ◽  
Endothelin 1

scholarly journals Aldosterone Inhibits Insulin-Induced Glucose Uptake by Degradation of Insulin Receptor Substrate (IRS) 1 and IRS2 via a Reactive Oxygen Species-Mediated Pathway in 3T3-L1 Adipocytes

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1662-1669 ◽  
Author(s):  
Tsutomu Wada ◽  
Satoshi Ohshima ◽  
Eriko Fujisawa ◽  
Daisuke Koya ◽  
Hiroshi Tsuneki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Glucocorticoid Receptor ◽  
Insulin Receptor ◽  
Receptor Antagonist ◽  
Glucose Uptake ◽  
Reactive Oxygen ◽  
Insulin Receptor Substrate ◽  
Oxygen Species ◽  
Metabolic Signaling

Serum aldosterone level is clinically known to correlate with body weight and insulin resistance. Because the underlying molecular mechanism is largely unknown, we examined the effect of aldosterone on insulin-induced metabolic signaling leading to glucose uptake in 3T3-L1 adipocytes. Aldosterone reduced the amounts of insulin receptor substrate (IRS) 1 and IRS2 in a time- and dose-dependent manner. As a result, insulin-induced phosphorylation of Akt-1 and -2, and subsequent uptake of 2-deoxyglucose were decreased. Degradation of IRSs was effectively prevented by a glucocorticoid receptor antagonist and antioxidant N-acetylcysteine, but not by a mineralocorticoid receptor antagonist. Because aldosterone induced phosphorylation of IRS1 at Ser307, responsible kinases were investigated, and we revealed that rapamycin and BMS345541, but neither SP600125 nor calphostin C, conferred for degradation of IRSs. Although lactacystin prevented the degradation of IRSs, glucose uptake was not preserved. Importantly, sucrose-gradient-sediment intracellular fraction analysis revealed that lactacystin did not effectively restore the reduction of IRS1 in the low-density microsome fraction, important for the transduction of insulin’s metabolic signaling. These results indicate that aldosterone deteriorates metabolic action of insulin by facilitating the degradation of IRS1 and IRS2 via glucocorticoid receptor-mediated production of reactive oxygen species, and activation of IκB Kinase β and target of rapamycin complex 1. Thus, aldosterone appears to be a novel key factor in the development of insulin resistance in visceral obesity.

scholarly journals Endothelin-1 mediates attenuated carotid baroreceptor activity by intermittent hypoxia

2012 ◽  
Vol 112 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Ying-Jie Peng ◽  
Jayasri Nanduri ◽  
Xin Zhang ◽  
Ning Wang ◽  
Gayatri Raghuraman ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Intermittent Hypoxia ◽  
Carotid Sinus ◽  
Reactive Oxygen ◽  
Male Rats ◽  
Oxygen Species ◽  
Arterial Baroreflex ◽  
Endothelin 1 ◽  
Carotid Baroreceptor ◽  
Baroreflex Function

The objectives of the present study were to examine the effects of intermittent hypoxia (IH) on arterial baroreflex function and assess the underlying mechanism(s). Experiments were performed on adult male rats treated with 14 days of IH (15 s of hypoxia, 5 min of normoxia; 8 h/day) or normoxia (control). Arterial blood pressures were elevated in IH-treated rats, and this effect was associated with attenuated heart rate and splanchnic sympathetic nerve responses to arterial baroreflex activation. In IH-treated rats, carotid baroreceptor responses to elevated sinus pressures were attenuated. Endothelin-1 (ET-1) levels were elevated in the carotid sinus region of IH-treated rats, and this effect was associated with increased endothelin converting enzyme (ECE) activity, which generates biologically active ET-1. ETA receptor antagonist prevented the effects of IH on carotid baroreceptor activity. In IH-treated rats, reactive oxygen species (ROS) levels were elevated in the carotid sinus region, and antioxidant treatment prevented the effects of IH on ET-1 levels, ECE activity, carotid baroreceptor activity, and baroreflex function. These results demonstrate that 1) IH attenuates arterial baroreflex function, which is in part due to reduced carotid baroreceptor responses to elevated carotid sinus pressure, and 2) IH-induced carotid baroreceptor dysfunction involves reactive oxygen species-dependent upregulation of ET-1 signaling in the carotid sinus region.

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