The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat

Zhang, Yi; Croft, Kevin D.; Mori, Trevor A.; Schyvens, Christopher G.; McKenzie, Katja U.S.; Whitworth, Judith A.

doi:10.1016/j.amjhyper.2003.11.004

Cited by 72 publications

(65 citation statements)

References 30 publications

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“…The hypothesis that oxidative stress contributes to arterial hypertension is supported by several lines of evidence: (1) the induction of oxidative stress by the administration of lead or the glutathione synthesis inhibitor, buthionine sulfoximine, or the SOD inhibitor, sodium diethyldithiocarbamate, increases blood pressure in rats [48,84]; (2) the infusion of H2O2 into the renal medulla leads to hypertension [48]; the treatment of hypertensive animals with antioxidants or inhibitors of ROS production prevents or attenuates hypertension [50,[85][86][87]; (3) the manipulation of genes related to ROS generation or elimination can alter blood pressure [88,89]; (4) the in vitro exposure of cells and tissues to exogenous oxidants reproduces events involved in the pathophysiology of hypertension [43]; (5) systemic and tissue redox dysfunction appears to precede the blood pressure elevation [90].…”

Section: Oxidative Stress As a Cause For Arterial Hypertensionmentioning

confidence: 99%

“…Since these factors may stimulate different redox pathways, the effectiveness of an antioxidant in one model does not necessarily translate to other models or to human essential hypertension which is known to have a multifactorial nature. Another important observation is that treatments with antioxidants or ROS inhibitors are generally more effective in preventing rather than reversing the hypertension [49,50,87,202]. Indeed, there are several studies demonstrating that ROS activate feed-forward mechanisms that amplify the cardiovascular and renal dysfunction [8,43,49,51].…”

Section: Targeting Oxidative Stress In Experimental Hypertensionmentioning

confidence: 99%

See 1 more Smart Citation

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Sousa¹,

Afonso²,

Albino‐Teixeira³

et al. 2012

Lipid Peroxidation

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Section: Oxidative Stress As a Cause For Arterial Hypertensionmentioning

confidence: 99%

Section: Targeting Oxidative Stress In Experimental Hypertensionmentioning

confidence: 99%

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Sousa¹,

Afonso²,

Albino‐Teixeira³

et al. 2012

Lipid Peroxidation

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“…10,11 However, data obtained in salt-induced or corticotropin (ACTH)-induced hypertension in rats indicate tempol-induced depressor effects are independent of endothelial function and oxidative stress. [12][13][14][15] Therefore, tempol-induced depressor effects may not be caused entirely by removal of O 2 Ϫ and/or increased NO availability. The present studies were performed to determine whether tempol directly causes vasodilation via an increased NO availability in DOCA-salt hypertensive rats.…”

Section: S Uperoxide Anion (Omentioning

confidence: 99%

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

Bian

Watts

et al. 2005

Hypertension

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Abstract-Large-conductance Ca 2ϩ -activated potassium (BK) channels modulate vascular smooth muscle tone. Tempol, a superoxide dismutase (SOD) mimetic, lowers blood pressure and inhibits sympathetic nerve activity in normotensive and hypertensive rats. In the present study, we tested the hypotheses depressor responses caused by tempol are partly mediated by vasodilation. It was found that tempol, but not tiron (a superoxide scavenger), dose-dependently relaxed mesenteric arteries (MA) in anesthetized sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Tempol also reduced perfusion pressure in isolated, norepinephrine (NE) preconstricted MA from sham and DOCA-salt hypertensive rats. Maximal responses in DOCA-salt rats were twice as large as those in sham rats. The vasodilation caused by tempol was blocked by iberiotoxin (IBTX, BK channel antagonist, 0.1 mol/L) and tetraethylammonium chloride (TEA) (1 mmol/L). Tempol did not relax KCl preconstricted arteries in sham or DOCA-salt rats, and N -nitro-L-arginine methyl ester (L-NAME), apamin, or glibenclamide did not alter tempol-induced vasodilation. IBTX constricted MA and this response was larger in DOCA-salt compared with sham rats. Western blots and immunohistochemical analysis revealed increased expression of BK channel ␣ subunit protein in DOCA-salt arteries compared with sham arteries. Whole-cell patch clamp studies revealed that tempol enhanced BK channel currents in HEK-293 cells transiently transfected with mslo, the murine BK channel a subunit. These currents were blocked by IBTX. The data indicate that tempol activates BK channels and this effect contributes to depressor responses caused by tempol. Upregulation of the BK channel ␣ subunit contributes to the enhanced depressor response caused by tempol in DOCA-salt hypertension. Ϫ ) increases blood pressure in hypertensive animals and humans in part by reducing the vascular bioavailability of nitric oxide (NO). 1 4-Hydroxy 2,2,6,6,-tetramethyl piperidine 1-oxyl (tempol), a superoxide dismutase (SOD) mimetic, lowers blood pressure in normotensive and hypertensive rats by multiple mechanisms. [2][3][4][5] Acute tempol treatment of normotensive, DOCA-salt and spontaneously hypertensive rats (SHRs) inhibits sympathetic nerve activity and this effect is not prevented by nitric oxide synthase (NOS) inhibition. 2-6 Local application of tempol onto renal sympathetic nerves decreased nerve activity without changing blood pressure (BP) or heart rate (HR). 7 The results suggested that changes in K ϩ channel activity might contribute to sympatho-inhibition caused by tempol. Central administration of tempol in normotensive rats reduced sympathetic nerve discharge 8,9 and attenuated sympathetic excitation caused by central angiotensin II administration. 9 Therefore, it is possible that tempol-induced vasodilation in vivo is masked by its sympatho-inhibitory effects. 9 Chronic tempol treatment attenuates blood pressure increases in hypertensive animals, an effect attributed to improvement in endothelium f...

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“…Augmented sensitivity and reactivity to angiotensin II and norepinephrine and subsequently increased vascular resistance have been defined following dexamethasone administration (16). The roles of oxidative stress and over-production of reactive oxygen species (ROS) through nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase pathway and nitric oxide (NO) deficiency have also been implicated in the pathophysiology of glucocorticoidinduced hypertension (17). Some antioxidant agents and herbal medicines have been able to prevent and reduce hypertension from dexamethasone in various investigations (18).…”

Section: Discussionmentioning

confidence: 99%

Portulaca oleracea seeds extract does not prevent dexamethasone-induced hypertension in rats

Safaeian¹,

Baniahmad²,

Esfandiari³

et al. 2017

J Herbmed Pharmacol

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The results of this study revealed that hydroalcoholic extract of P. oleracea seeds aggregates hypertension in dexamethasoneinduced hypertensive rats. Therefore, it is recommended that its using be avoided in hypertensive patients receiving glucocorticoids. Please cite this paper as: Introduction:Portulaca oleracea is used as a nutritional and medicinal plant. The aim of this study was to assess the effect of hydroalcoholic extract of P. oleracea seeds in dexamethasone -induced hypertension in rats. Methods: For induction of hypertension, dexamethasone (30 µg/kg/d, subcutaneously) was administered for 14 days. Animals received P. oleracea extract as a pretreatment at various doses of 100, 200 and 400 mg/kg/d orally from 4 days before dexamethasone administration and during the test period. Systolic blood pressure (SBP) and heart rate were measured using tailcuff method. The weight of thymus gland was estimated as a marker of glucocorticoid activity. Results: Dexamethasone injection significantly increased SBP (P < 0.001) while decreased the body and thymus weights (P < 0.05 and P < 0.001, respectively). Oral administration of P. oleracea could not prevent rising in SBP and decreasing in thymus weight. It also increased heart rate in hypertensive rats at the dose of 400 mg/kg/d (P < 0.05). Conclusion:The results of this study revealed that hydroalcoholic extract of P. oleracea seeds aggregates hypertension in dexamethasone-induced hypertensive rats. Hence, it should be used with caution in hypertensive patients receiving glucocorticoids.

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The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat

Cited by 72 publications

References 30 publications

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Lipid Peroxidation and Antioxidants in Arterial Hypertension

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

Portulaca oleracea seeds extract does not prevent dexamethasone-induced hypertension in rats

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