Malfunction of Vascular Control in Lifestyle-Related Diseases: Oxidative Stress of Angiotensin II-induced Hypertension: Mitogen-Activated Protein Kinases and Blood Pressure Regulation

Kimura, Shoji; Zhang, Guoxing; Abe, Youichi

doi:10.1254/jphs.fmj04006x5

Cited by 20 publications

(16 citation statements)

References 25 publications

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“…Oxidative stress resulting from the accumulation of reactive oxygen species (ROS) is well characterized in diabetic complications (6,7). MG induces oxidative stress by inactivating antioxidant enzymes such as Cu, Zn-superoxide dismutase and glutathione (GSH) peroxidase (8,9).…”

Section: Introductionmentioning

confidence: 99%

Methylglyoxal Causes Dysfunction of Thioredoxin and Thioredoxin Reductase in Endothelial Cells

et al. 2009

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Abstract. Methylglyoxal (MG), a reactive dicarbonyl produced during glucose metabolism, induces oxidative stress and apoptosis. Under hyperglycemic conditions, the abnormal accumulation of MG is related to the development of diabetic complications. We examined the effects of MG on thioredoxin (Trx) and glutaredoxin (Grx) systems, two thiol-disulfide oxidoreductase systems that protect against oxidative damage of proteins, in bovine aortic endothelial cells (BAECs). The levels of protein carbonyls as markers of protein oxidation increased in BAECs exposed to MG at 5 mM, resulting in the loss of cell viability. Western blot analysis demonstrated that Trx protein level decreased when BAECs were exposed to 5 mM MG. MG also inactivated Trx reductase, which maintains Trx in the reduced/active state. Moreover, peroxiredoxin, which is dependent on Trx and Trx reductase to maintain its reduced state, was oxidized by 5 mM MG. No significant difference in the levels of Trx, Trx reductase, or peroxiredoxin was observed in BAECs exposed to MG at 1 mM; this concentration had little effect on protein carbonyl formation and cell viability. MG failed to decrease Grx activity, indicating that Trx is more susceptible to MG than Grx. Taken together, these findings suggest that MG causes dysfunction of the Trx system, including Trx and Trx reductase, in BAECs.

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Section: Introductionmentioning

confidence: 99%

Methylglyoxal Causes Dysfunction of Thioredoxin and Thioredoxin Reductase in Endothelial Cells

et al. 2009

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“…Association between protein S-nitrosation and diseases such as diabetes (2,30) has been reported but association with other CVDs such as hypertension has not been directly addressed. Angiotensin II (ANG II) is a peptide involved in blood pressure regulation and renovascular hypertension (11,14,18) and elevated levels of ANG II induce hypertension. ANG II infusion or treatment, which is clearly established as an inducer of oxidative stress via activation of NADPH oxidases in vivo (17) and in vascular smooth muscle cells such as A7r5 (31), was recently reported to generate global S-nitrosation (3).…”

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confidence: 99%

Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model

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Huang

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model. Am J Physiol Heart Circ Physiol 303: H597-H604, 2012. First published June 22, 2012; doi:10.1152/ajpheart.00138.2012 by activating soluble guanylyl cyclase (sGC) is involved in vascular homeostasis via induction of smooth muscle relaxation. In cardiovascular diseases (CVDs), endothelial dysfunction with altered vascular reactivity is mostly attributed to decreased NO bioavailability via oxidative stress. However, in several studies, relaxation to NO is only partially restored by exogenous NO donors, suggesting sGC impairment. Conflicting results have been reported regarding the nature of this impairment, ranging from decreased expression of one or both subunits of sGC to heme oxidation. We showed that sGC activity is impaired by thiol S-nitrosation. Recently, angiotensin II (ANG II) chronic treatment, which induces hypertension, was shown to generate nitrosative stress in addition to oxidative stress. We hypothesized that S-nitrosation of sGC occurs in ANG II-induced hypertension, thereby leading to desensitization of sGC to NO hence vascular dysfunction. As expected, ANG II infusion increases blood pressure, aorta remodeling, and protein S-nitrosation. Intravital microscopy indicated that cremaster arterioles are resistant to NO-induced vasodilation in vivo in anesthetized ANG II-treated rats. Concomitantly, NO-induced cGMP production decreases, which correlated with S-nitrosation of sGC in hypertensive rats. This study suggests that S-nitrosation of sGC by ANG II contributes to vascular dysfunction. This was confirmed in vitro by using A7r5 smooth muscle cells infected with adenoviruses expressing sGC or cysteine mutants: ANG II decreases NO-stimulated activity in the wild-type but not in one mutant, C516A. This result indicates that cysteine 516 of sGC mediates ANG II-induced desensitization to NO in cells. nitric oxide resistance; vascular dysfunction; oxidative stress; hypertension SOLUBLE GUANYLYL CYCLASE (sGC) is the main receptor for nitric oxide (NO) and the enzyme responsible for the conversion of GTP into cGMP. As such, the NO-receptor sGC is crucially involved in the physiology of the cardiovascular system by modulating vessel tone. Indeed, mice lacking this receptor are hypertensive (5). Oxidative stress is associated with cardiovascular diseases (CVDs) such as hypertension, atherosclerosis, and diabetes. Most oxidative CVDs are accompanied by endothelial dysfunction and impaired vascular reactivity with decreased NO bioavailability. Nonetheless, it should be pointed out that oxidative stress affects as well the smooth muscle cell (SMC) layers where sGC is expressed. It has been reported that reactive oxygen species (ROS) alter sGC expression and activity (19,25,29). We (21) have previously shown that in vitro and in vivo S-nitrosation of sGC impairs its ability to be activated by NO. In particular, we established that infusion of low therapeutic doses of nitroglycerin in rats for 3 days i...

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“…Ang II is known to activate MAPKs, in particular ERK1/2, which is as-sociated with development of hypertension and cardiac hypertrophy [48] . Very recently it was reported that p38MAPK regulates the activities of NADPH oxidase and eNOS and thereby may infl uence NO bioavailability [49] .…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Nitric Oxide-Sparing Actions of Dihydropyridines and ACE Inhibitors Differ in Human Endothelial Cells

et al. 2005

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The effects of dihydropyridine Ca²⁺ channel blockers (DHP) and ACE inhibitors on superoxide formation and nitric oxide (NO) bioavailability were compared in human EA.Hy926 endothelial cells (EC). EC were stimulated 4 h with angiotensin II (Ang II, 10 nM) ± study drugs. Specific superoxide formation was measured by lucigenin-enhanced chemiluminescence, reduction of cytochrome c and rhodamine-123 fluorescence. Free NO release was determined with an amperometric NO sensor. NADPH oxidase subunits expression was examined with Western Blot. In untreated EC the intracellular superoxide is –64.3 ± 6.0% decreased compared to Ang II stimulated EC. Elevated extracellular superoxide formation was on a –43.0 ± 1.7% lower level in untreated EC. The DHP Ca²⁺-channel agonist BayK8644 and ACE inhibitors captopril and ramiprilat led extracellular superoxide concentration to control level. Enalaprilat blocked extracellular superoxide, the DHP amlodipine and nisoldipine prevented intracellular increases only (n = 8–9, p < 0.05). Icatibant (HOE 140), a kinin-B₂ receptor antagonist, attenuated antioxidant actions of all tested agents except of nisoldipine. Ang II-induced superoxide was elevated by the phorbolester PMA and blocked by the protein kinase C (PKC) inhibitor chelerythrine. Suppression of substance P-evoked NO release by Ang II (>70%, n = 6) was reversed by the PKC inhibitor chelerythrine, the DHP amlodipine and nisoldipine and the ACE inhibitor ramiprilat. Further, Ang II reduces Nox-4 expression by 34.5 ± 4.9. Nox-2 expression was not regulated. DHP and ACE inhibitors exert different antioxidant effects in human EC stimulated with Ang II, but both improve NO bioavailability via bradykinin and modulation of redox-regulating enzymes.

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Malfunction of Vascular Control in Lifestyle-Related Diseases: Oxidative Stress of Angiotensin II-induced Hypertension: Mitogen-Activated Protein Kinases and Blood Pressure Regulation

Cited by 20 publications

References 25 publications

Methylglyoxal Causes Dysfunction of Thioredoxin and Thioredoxin Reductase in Endothelial Cells

Methylglyoxal Causes Dysfunction of Thioredoxin and Thioredoxin Reductase in Endothelial Cells

Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model

Antioxidant and Nitric Oxide-Sparing Actions of Dihydropyridines and ACE Inhibitors Differ in Human Endothelial Cells

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