Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

Dobrian, Anca D.; Schriver, Suzanne D.; Khraibi, Ali A.; Prewitt, Russell L.

doi:10.1161/01.hyp.0000103629.01745.59

Cited by 174 publications

(122 citation statements)

References 43 publications

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“…Several lines of evidence have shown that PPAR γ ligands stimulate NO production both in vitro ( 13 ) and in vivo ( 14 ). We have also demonstrated that in obese Zucker rats, in which renal NOx production is suppressed compared with that in lean Zucker rats, troglitazone causes partial restoration of urinary NOx excretion ( 31 ).…”

Section: Discussionsupporting

confidence: 56%

“…Several lines of evidence have demonstrated that PPARγ ligands not only improve insulin resistance, but also exert multiple actions, including antihypertensive actions and anti-inflammatory actions (12). PPARγ ligands have also been reported to increase NO production in various tissues by multiple mechanisms (13,14). However, the effects of PPARγ ligands on ADMA production and the resultant NO production have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Pioglitazone Lowers Systemic Asymmetric Dimethylarginine by Inducing Dimethylarginine Dimethylaminohydrolase in Rats

et al. 2005

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Pioglitazone Lowers Systemic Asymmetric Dimethylarginine by Inducing Dimethylarginine Dimethylaminohydrolase in Rats

et al. 2005

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“…1,2 The NADPH oxidase NADPH oxidase and obesity-induced neointima J-X Chen and A Stinnett subunit proteins (gp91 phox p22 phox and p67 phox ) are increased in animal models of obesity and in the internal mammary arteries of patients with diabetes 4,26,27 In obese mice, treatment with apocynin reduces ROS production in adipose tissue, attenuates the dysregulation of adipocytokines. 28 Previous studies also implicates that insulin resistance is closely associated with oxidative stress.…”

Section: Disscussionmentioning

confidence: 99%

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Chen

Stinnett

2008

Laboratory Investigation

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Reactive oxygen species (ROS) formation is associated with inflammation and vasculature dysfunction. We investigated the potential role of the NADPH oxidase on vascular Toll-like receptor (TLR) expression and carotid neointimal formation in high-fat (HF) diet-induced obesity (DIO) model. Using mice DIO and common carotid artery flow cessation-induced lesion formation models, we examined vascular TLR2 and TLR4 expression and neointimal formation in NADPH oxidase subunit p47 phox -deficient (p47 phox-/-) mice. Feeding C57BL/6J mice an HF diet for 22 weeks resulted in significant increases in p47 phox , TLR2 and TLR4 expression in vascular tissues compared with mice fed a low-fat (LF) diet. Minimal changes in TLR2 and TLR4 expression was detected in p47 phox-/-DIO mice. Furthermore, flow cessation-induced angiogenic and inflammatory response and neointimal formation were significantly attenuated in p47 phoxÀ/À DIO mice compared with wild-type DIO mice. In addition, exposure of endothelial cells to leptin led to ROS formation; this was accompanied by upregulation of TLR2, TLR4 expression and its downstream signaling. Leptin also increased endothelial cell migration and proliferation. Pharmacological inhibition of NADPH oxidase or genetic deletion of p47 phox significantly diminished these alterations. Obesity increases neointimal formation via a mechanism involving p47 phox -TLRs signaling, suggesting that the NADPH oxidase may represent a potential novel therapeutic target for the treatment of obesity-associated vascular inflammation and dysfunction.

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“…Several drugs may have a marked impact on NO production. Dobrian et al 86 recently reported that the peroxisome proliferator-activated receptor-␥ agonist and insulin sensitizer pioglitazone prevented the development of hypertension in obese hypertensive rats. This therapeutic effect was at least partially attributed to increased renal NO production and bioavailability caused by decreased superoxide generation.…”

Section: Other Regulators Of Nos Activitymentioning

confidence: 99%

Recent Advances in the Regulation of Nitric Oxide in the Kidney

Herrera

Garvin

2005

Hypertension

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Abstract-Nitric oxide (NO) plays important roles in the regulation of renal function and the long-term control of blood pressure. New roles of NO have been proposed recently in diabetes, nephrotoxicity, and pregnancy. NO derived from all 3 NOS isoforms contributes to the overall regulation of kidney function, and recent advances in our understanding of their regulation have been made lately. In this regard, substrate and cofactor availability play important roles in regulating nitric oxide synthase (NOS) activity not only by limiting enzyme activity but also by influencing the coupling of NOS with its cofactors, tetrahydrobiopterin and NADPH. Protein-protein interactions are now recognized to be important negative and positive regulators of NOS. Phosphorylation is another component of the mechanism whereby NOS is activated or deactivated. Increased NOS expression can also influence enzyme activity; however, the degree of expression does not always correlate with enzyme activity because increased NO levels can result in inhibition of NOS. Finally, other potential regulators of NOS such as endogenous L-arginine analogs may also be important. In this article, we summarize recent advances in the regulation of activity and expression of the NOS isoforms within the kidney. renal function and long-term regulation of blood pressure. [1][2][3][4] This is best evidenced by the fact that inhibiting intrarenal NO production increased blood pressure. 5 In addition, reduced NO has been identified as a common denominator of many hypertensive models. 6 -9 The effects of NO on blood pressure via actions in the kidney occur through multiple mechanisms. These include increasing renal blood flow caused by vasodilatation, 10 increasing glomerular filtration, 11 inhibiting sodium transport along the nephron, 12-14 and regulating release of renin. 15 NO produced by each of the 3 nitric oxide synthases (NOS), NOS 1, NOS 2, and NOS 3, reportedly contributes to the regulation of renal function. Inhibition of NOS activity within the kidney is known to lead to sodium retention and hypertension. This review addresses recent advances in our understanding of the role played by renal NO in various physiological and pathophysiological conditions, as well as how NO production is regulated. Roles for Renal NOHistorically, NO produced by the kidney has been thought of primarily as a factor that regulates urinary volume and sodium excretion. The physiological effects of NO can be mediated via changes in renal hemodynamics and/or salt and water absorption by the nephron. NO reduces renal vascular tone in part by dilating the afferent arteriole. 16 It also increases glomerular filtration rate. 11 NO modulates renin secretion by the juxtaglomerular apparatus 15 and tubuloglomerular feedback. 3 Finally, NO regulates transport in various nephron segments as reviewed recently by Ortiz and Garvin. 12 More recently it has been recognized that in a number of pathophysiological conditions, the actions of NO on renal hemodynamics and/or nephron transport are ...

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Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

Cited by 174 publications

References 43 publications

Pioglitazone Lowers Systemic Asymmetric Dimethylarginine by Inducing Dimethylarginine Dimethylaminohydrolase in Rats

Pioglitazone Lowers Systemic Asymmetric Dimethylarginine by Inducing Dimethylarginine Dimethylaminohydrolase in Rats

Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high-fat diet-induced obesity

Recent Advances in the Regulation of Nitric Oxide in the Kidney

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