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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.
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PMID:Role of xanthine oxidase in dexamethasone-induced hypertension in rats. 1743 25

Suaeda asparagoides Miq. (Chenopodiaceae: S. asparagoides) is a salt-marsh plant that has long been prescribed in traditional Oriental medicine for the treatment of hypertension and hepatitis. In order to elucidate the pharmacological mechanisms of the herb, we conducted an examination of the anti-oxidative and anti-inflammatory properties of solvent-extracts of S. asparagoides. All of the solvent fractions showed potent anti-oxidative effects, as assessed using a radical generation assay system (xanthine oxidase assay) and an electron-donating activity system (DPPH [2,2-diphenyl-l-picrylhydrazyl radical] assay), with IC50 values ranging from 9 to 42 microg/ml. In agreement with this pattern, the total phenolic contents were widely distributed in the various solvent fractions, and ranged from 36.5 to 50.3 mg/g of dry weight. All of the solvent fractions significantly suppressed NO production in RAW264.7 cells induced by lipopolysaccharide (LPS, 0.1 microg/ml) and of the fractions, only the chloroform (CHC) fraction completely blocked the expression of inducible NO synthase (iNOS). Additionally, the hexane (HEX) and CHC fractions suppressed the mRNA expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) and monocyte chemoattractant protein 1 (MCP-1), respectively, in the LPS-stimulated RAW264.7 cells. Therefore, these results suggest that the pharmacological action of S. asparagoides is due to its potent anti-oxidative effects and anti-inflammatory effects, and that therefore it can be applied to other diseases caused by oxidative stress and inflammation, such as cardiovascular diseases.
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PMID:In vitro anti-oxidative and anti-inflammatory effects of solvent-extracted fractions from Suaeda asparagoides. 1766 94

A large body of literature suggest that vascular reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases are important sources of reactive oxygen species. Many studies, however, relied on data obtained with the inhibitor apocynin (4'-hydroxy-3'methoxyacetophenone). Because the mode of action of apocynin, however, is elusive, we determined its mechanism of inhibition on vascular NADPH oxidases. In HEK293 cells overexpressing NADPH oxidase isoforms (Nox1, Nox2, or Nox4), apocynin failed to inhibit superoxide anion generation detected by lucigenin chemiluminescence. In contrast, apocynin interfered with the detection of reactive oxygen species in assay systems selective for hydrogen peroxide or hydroxyl radicals. Importantly, apocynin interfered directly with the detection of peroxides but not superoxide, if generated by xanthine/xanthine oxidase or nonenzymatic systems. In leukocytes, apocynin is a prodrug that is activated by myeloperoxidase, a process that results in the formation of apocynin dimers. Endothelial cells and smooth muscle cells failed to form these dimers and, therefore, are not able to activate apocynin. Dimer formation was, however, observed in Nox-overexpressing HEK293 cells when myeloperoxidase was supplemented. As a consequence, apocynin should only inhibit NADPH oxidase in leukocytes, whereas in vascular cells, the compound could act as an antioxidant. Indeed, in vascular smooth muscle cells, the activation of the redox-sensitive kinases p38-mitogen-activate protein kinase, Akt, and extracellular signal-regulated kinase 1/2 by hydrogen peroxide and by the intracellular radical generator menadione was prevented in the presence of apocynin. These observations indicate that apocynin predominantly acts as an antioxidant in endothelial cells and vascular smooth muscle cells and should not be used as an NADPH oxidase inhibitor in vascular systems.
Hypertension 2008 Feb
PMID:Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. 1808 48

Increased fructose consumption is associated with hyperuricemia, metabolic syndrome, and renal damage. This study evaluated whether febuxostat (Fx), an investigational nonpurine, and selective xanthine oxidase inhibitor, could alleviate the features of metabolic syndrome as well as the renal hemodynamic alterations and afferent arteriolopathy induced by a high-fructose diet in rats. Two groups of rats were fed a high-fructose diet (60% fructose) for 8 wk, and two groups received a normal diet. For each diet, one group was treated with Fx (5-6 mg.kg(-1).day(-1) in the drinking water) during the last 4 wk (i.e., after the onset of metabolic syndrome), and the other received no treatment (placebo; P). Body weight was measured daily. Systolic blood pressure and fasting plasma uric acid (UA), insulin, and triglycerides were measured at baseline and at 4 and 8 wk. Renal hemodynamics and histomorphology were evaluated at the end of the study. A high-fructose diet was associated with hyperuricemia, hypertension, as well as increased plasma triglycerides and insulin. Compared with fructose+P, fructose+Fx rats showed significantly lowered blood pressure, UA, triglycerides, and insulin (P < 0.05 for all comparisons). Moreover, fructose+Fx rats had significantly reduced glomerular pressure, renal vasoconstriction, and afferent arteriolar area relative to fructose+P rats. Fx treatment in rats on a normal diet had no significant effects. In conclusion, normalization of plasma UA with Fx in rats with metabolic syndrome alleviated both metabolic and glomerular hemodynamic and morphological alterations. These results provide further evidence for a pathogenic role of hyperuricemia in fructose-mediated metabolic syndrome.
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PMID:Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. 1821 51

Oxidative stress is a common denominator in many aspects of the pathogenesis of atherosclerosis and cardiovascular diseases. Some drugs, such as vitamin C, vitamin E, and a free radical scavenger, edaravone, are prescribed with oxidative stress as their main target. Furthermore, of the drugs in current clinical use, such as anti-hypertension reagents including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB), and anti-hyperlipidemic reagents like statins, protect various organs, e.g., vessel, brain, heart, and kidney, via anti-oxidative stress effects in addition to their original pharmacological properties. While results of clinical trials of anti-oxidative stress reagents in patients with cardiovascular disease are contradictory to date, this may be explained by a variety of reasons such as an inadequate study design. More competent anti-oxidative reagents are awaited, and superoxide dismutase mimetics, thiols, xanthine oxidase and NAD(P)H oxidase inhibitors, which regulate intracellular redox reaction and subsequently inhibit oxidative stress, are among promising candidates of future drug developments currently receiving much interest. In this review, the current advances will be highlighted in development of novel anti-oxidative therapeutic approaches against cardiovascular diseases.
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PMID:Oxidative stress in cardiovascular disease: a new avenue toward future therapeutic approaches. 1822 Oct 82

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.
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PMID:NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. 1822 81

1. There is increasing evidence for a role of oxidative stress and nitric oxide deficiency in experimental glucocorticoid-induced hypertension, as evidenced by increased biomarkers of oxidative stress; the effectiveness of antioxidants or reduced NADPH oxidase antagonists in lowering blood pressure; and secondary upregulation of endogenous antioxidant enzymes in response to oxidative stress. 2. In the vasculature, the main sources of superoxide are NADPH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase (eNOS) and mitochondria. 3. NADPH oxidase plays a significant role in the pathogenesis of glucocorticoid-induced hypertension in the rats, but xanthine oxidase and uncoupled eNOS pathways are not important sources of reactive oxygen species in these models. The role of mitochondrial reactive oxygen species in glucocorticoid-induced hypertension remains to be clarified.
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PMID:Reactive oxygen species and glucocorticoid-induced hypertension. 1830 45

Oxidative stress plays an important role in the pathogenesis of hypertension. A number of sources of reactive oxygen species have been identified including NADPH oxidase, endothelial NO synthase, and xanthine oxidase. Inhibitors of these systems reduce blood pressure in experimental models. Targeted overexpression of antioxidant systems and interference with expression of oxidant systems has also been successfully used in animal models of hypertension. It is expected that these strategies will eventually be translated to human disease, but currently, the specificity and toxicity of such measures are not yet fulfilling quality criteria for treatment of humans. In the meantime, presumably nontoxic measures, such as administration of antioxidant vitamins, are the only available treatments for oxidative stress in humans. In this review, we discuss strategies to target oxidative stress both in experimental models and in humans. We also discuss how patients could be selected who particularly benefit from antioxidant treatment. In clinical practice, diagnostic procedures beyond measurement of blood pressure will be necessary to predict the response to antioxidants; these procedures will include measurement of antioxidant status and detailed assessment of vascular structure and function.
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PMID:Targeting reactive oxygen species in hypertension. 1832 Dec 2

Endothelial dysfunction in the setting of cardiovascular risk factors such as hypercholesterolemia, diabetes mellitus, chronic smoking, as well hypertension, is, at least in part, dependent of the production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO). ROS-producing enzymes involved in increased oxidative stress within vascular tissue include NADPH oxidase, xanthine oxidase, and mitochondrial superoxide producing enzymes. Superoxide produced by the NADPH oxidase may react with NO, thereby stimulating the production of the NO/superoxide reaction product peroxynitrite. Peroxynitrite in turn has been shown to uncouple eNOS, therefore switching an antiatherosclerotic NO producing enzyme to an enzyme that may accelerate the atherosclerotic process by producing superoxide. Increased oxidative stress in the vasculature, however, is not restricted to the endothelium and also occurs within the smooth muscle cell layer. Increased superoxide production has important consequences with respect to signaling by the soluble guanylate cyclase and the cGMP-dependent kinase I, which activity and expression is regulated in a redox-sensitive fashion. The present review will summarize current concepts concerning eNOS uncoupling, with special focus on the role of tetrahydrobiopterin in mediating eNOS uncoupling.
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PMID:Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. 1832 Dec 9

Endothelial dysfunction (ED) in the setting of cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, chronic smoking as well as in patients with heart failure has been shown to be at least in part dependent on the production of reactive oxygen species (ROS) such as superoxide and the subsequent decrease in vascular bioavailability of nitric oxide (NO). Methods to quantify endothelial dysfunction include forearm plethysmography, flow-dependent dilation of the brachial artery, finger-pulse plethysmography, pulse curve analysis, and quantitative coronary angiography after intracoronary administration of the endothelium-dependent vasodilator acetylcholine. Superoxide sources include the NADPH oxidase, xanthine oxidase, and mitochondria. Superoxide produced by the NADPH oxidase may react with NO released by the endothelial nitric oxide synthase (eNOS) thereby generating peroxynitrite (ONOO-), leading to eNOS uncoupling and therefore eNOS-mediated superoxide production. The present review will discuss current concepts of how to assess endothelial function, prognostic implications of ED, mechanisms underlying ED with focus on oxidative stress and circulating biomarkers, which have been proposed to indicate endothelial dysfunction and/or damage, respectively.
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PMID:Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. 1838 84


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