Apocynin but Not l-Arginine Prevents and Reverses Dexamethasone-Induced Hypertension in the Rat

Hu, Lexian; Zhang, Yi; Lim, Pek Siew; Miao, Youzhi; Tan, Chrismin; McKenzie, Katja U.S.; Schyvens, Christopher G.; Whitworth, Judith A.

doi:10.1016/j.amjhyper.2005.09.023

Cited by 76 publications

(57 citation statements)

References 28 publications

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“…In this study, DEX-HT was not associated with any change in hematocrit. This finding was different from that reported by Hu et al 5 and Tonolo et al 13 showing that DEX at lower doses (20 mg kg À1 per day, which is approximately 5-6 mg per rat per day and 2 mg per rat per day) resulted in a small but significant increase in hematocrit in rats. It is possible that the small increase in hematocrit due to DEX treatment in this study was masked by interventions during surgical procedures, such as intravenous saline administration.…”

Section: Discussioncontrasting

confidence: 56%

“…The roles of endogenous vasoconstrictors and vasodilators in DEX-HT are variable, with possible associations with nitric oxide, prostanoids, angiotensin II, arginine vasopressin, endothelins, catecholamines, neuropeptide Y and atrial natriuretic peptide. 1 Studies on DEX-HT in rodents have indicated that nitric oxide deficiency 4 and oxidative stress 5 are implicated in this form of hypertension. Nevertheless, the hemodynamic profile has not been fully evaluated in this model.…”

Section: Introductionmentioning

confidence: 99%

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Hemodynamics of dexamethasone-induced hypertension in the rat

et al. 2009

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Although dexamethasone (DEX) is known to cause hypertension in humans and in animals, the hemodynamic characteristics of DEX-induced hypertension (DEX-HT) in the rat remain unclear. This study evaluated central and regional hemodynamics, and the role of total peripheral resistance (TPR) using a vasodilator minoxidil. Rats were divided into four groups, namely saline (n¼20), DEX (n¼21), minoxidil+saline (n¼10) and minoxidil+DEX (n¼10). Tail-cuff systolic blood pressure was recorded every second day. After 10-14 days of treatment, central (saline: n¼9, DEX: n¼10) and regional (saline: n¼11, DEX: n¼11) hemodynamic parameters were measured. Central hemodynamic data were also obtained from minoxidil-treated rats. DEX increased blood pressure (Po0.0005) in association with an increase in TPR (Po0.05). However, individual assessments of renal, mesenteric and hindquarter circulations did not detect any significant increase in resistance in these beds. Minoxidil increased cardiac output (P ¢o0.01) and cardiac index (P ¢o0.005) as well as decreased TPR (P¢o0.05) without affecting DEX-HT. DEX prevented weight gain and decreased thymus weight. The increase in TPR in DEX-HT in rats was not simply explained by isolated alterations to resistance in the renal, mesenteric or hindquarter circulations. Minoxidil effectively prevented the increase in TPR but not the increase in blood pressure, suggesting that an increase in TPR is not essential for DEX-induced blood pressure increase. Keywords: dexamethasone; hemodynamics; minoxidil; total peripheral resistance INTRODUCTION Synthetic glucocorticoid dexamethasone (DEX) is commonly used in clinical settings for the treatment of various medical conditions. It is used in adrenal insufficiency as a glucocorticoid hormone replacement treatment, in multiple myeloma together with other chemotherapeutic agents, to decrease cerebral edema due to intracranial pathology and as an anti-emetic in patients with cancer. When used chronically at a supra-physiological dose, DEX results in hypertension. The underlying mechanism for DEX-induced hypertension (DEX-HT) remains unclear. We have recently reviewed postulated mechanisms of DEX-HT. 1 There is evidence against plasma volume expansion 2 or sympathetic nerve activation 3 as key mechanisms of DEX-HT in humans. The roles of endogenous vasoconstrictors and vasodilators in DEX-HT are variable, with possible associations with nitric oxide, prostanoids, angiotensin II, arginine vasopressin, endothelins, catecholamines, neuropeptide Y and atrial natriuretic peptide. 1 Studies on DEX-HT in rodents have indicated that nitric oxide deficiency 4 and oxidative stress 5 are implicated in this form of hypertension. Nevertheless, the hemodynamic profile has not been fully evaluated in this model.The hemodynamics of DEX-HT has been evaluated in both humans 6 and dogs. 7 DEX-HT in humans (3 mg per day) was associated with increased total peripheral resistance (TPR) without any

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Hemodynamics of dexamethasone-induced hypertension in the rat

et al. 2009

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“…On the other hand, overexpression of vascular p22phox was associated with increased oxidative stress and vascular dysfunction but no significant increase in blood pressure (79). Treatment with apocynin or diphenylene iodinium, pharmacological inhibitors of NAD(P)H oxidase, or gp91ds-tat, a novel specific inhibitor of NAD(P)H oxidase, reduced vascular ⅐O 2 Ϫ production, prevented cardiovascular remodeling, and attenuated development of hypertension in Ang II-treated mice (74,80,81). In most of these models, Ang II was infused for a short time period (1-3 weeks), inducing an acute hypertensive response.…”

Section: Nad(p)h Oxidase Oxidative Stress and Hypertensionmentioning

confidence: 99%

NADPH Oxidases, Reactive Oxygen Species, and Hypertension

2008

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Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization, and cellular signaling. Increased ROS production (termed "oxidative stress") has been implicated in various pathologies, including hypertension, atherosclerosis, diabetes, and chronic kidney disease. A major source for vascular and renal ROS is a family of nonphagocytic NAD(P)H oxidases, including the prototypic Nox2 homolog-based NAD(P)H oxidase, as well as other NAD(P)H oxidases, such as Nox1 and Nox4. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase, and uncoupled nitric oxide synthase. NAD(P)H oxidase-derived ROS plays a physiological role in the regulation of endothelial function and vascular tone and a pathophysiological role in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, important processes underlying cardiovascular and renal remodeling in hypertension and diabetes. These findings have evoked considerable interest because of the possibilities that therapies against nonphagocytic NAD(P)H oxidase to decrease ROS generation and/or strategies to increase nitric oxide (NO) availability and antioxidants may be useful in minimizing vascular injury and renal dysfunction and thereby prevent or regress target organ damage associated with hypertension and diabetes. Here we highlight current developments in the field of reactive oxygen species and cardiovascular disease, focusing specifically on the recently identified novel Nox family of NAD(P)H oxidases in hypertension. We also discuss the potential role of targeting ROS as a therapeutic possibility in the management of hypertension and cardiovascular disease.Diabetes Care 31 (Suppl. 2):S170-S180, 2008

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“…Antihypertensive effect Lack of antihypertensive effect Apocynin Prevented/attenuated mineralocorticoid-induced hypertension [86,240] Prevented/reversed glucocorticoid-induced hypertension [241] Prevented/reversed adrenocorticotropic hormone-induced hypertension [242] Prevented the development of Ang II-induced hypertension in mice [186] Prevented the development of renovascular hypertension [243] Prevented the development of hypertension induced by RAS activation [50] Reduced blood pressure in borderline and spontaneous hypertension [244] Attenuated salt-sensitive hypertension [245] Normalized blood pressure in a model of hypertension induced by disruption of dopamine D2 receptor [246] Failed to prevent the hypertension induced by chronic infusion of endothelin-1 [200] Failed to prevent hypertension in transgenic mice overexpressing renin or angiotensinogen [247,248] Failed to prevent Ang II-induced hypertension in rats [249,250] Gp91ds-tat Attenuated the blood pressure rise induced by Ang II in mice [209] Failed to attenuate salt-sensitive hypertension [251] Allopurinol Attenuated salt-sensitive hypertension [252] Prevented glucocorticoid-induced hypertension [253] Failed to prevent or attenuate mineralocorticoid-induced hypertension [254] Failed to prevent glucocorticoidinduced hypertension [255] Failed to prevent or attenuate adrenocorticotropic-induced hypertension [242] Failed to prevent the development of hypertension induced by the blockade of nitric oxide synthesis [256] Failed to prevent the progression of hypertension in young SHR [257] Oxypurinol Reduced blood pressure in SHR [258] Tempol Attenuated hypertension in SHR [201] Prevented the progression of hypertension in saltloaded SHRSP [259] Attenuated mineralocorticoid-induced hypertension [260] Failed to prevent Ang II-induced hypertension [264] Failed to attenuate hypertension induced by inhi...…”

Section: Drugmentioning

confidence: 99%