Upregulation of p67phoxand gp91phoxin aortas from angiotensin II-infused mice

Cifuentes, Maria; Rey, Federico E.; Carretero, Oscar A.; Pagano, Patrick J.

doi:10.1152/ajpheart.2000.279.5.h2234

Cited by 163 publications

(138 citation statements)

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“…5,11 In this article, we demonstrate that GLUT4 expression is decreased in the aorta in the established mouse model of Ang IImediated hypertension, [22][23][24] that this model of hypertension is associated with potentiated 5-HT contraction, and that inhibition of GLUT4 does not affect VSMC contractility in the aortas from the hypertensive animals as greatly as it occurs in the aortas from the normotensive animals ( Figure 6). These observations corroborate and extend our previous findings in aortas from DOCA-salt hypertensive rats 5 and demonstrate a pathophysiological correlation between decreased GLUT4 expression and potentiated VSMC contractility associated with hypertension.…”

Section: Discussionmentioning

confidence: 89%

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GLUT4 Facilitative Glucose Transporter Specifically and Differentially Contributes to Agonist-Induced Vascular Reactivity in Mouse Aorta

Park

Loberg

Duquaine

et al. 2005

ATVB

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Objective-We hypothesized that GLUT4 is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction. Methods and Results-Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, Ϸ50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F 2␣ -mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4. Conclusions-Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension. Key Words: glucose Ⅲ GLUT4 Ⅲ indinavir Ⅲ vascular smooth muscle M ammalian cells use glucose for the generation of ATP through oxidative and nonoxidative metabolism, but because the lipid bilayer of cellular membranes is impermeable to carbohydrates, the cell must rely on a system of hexose transporters to facilitate uptake of these sugars. To date, at least 13 facilitative glucose transporters have been cloned. 1 The GLUT transporters are homologous glycosylated polypeptides with distinct substrate specificity, affinity, and tissue distribution. 2 GLUT4 is considered the major insulin-responsive transporter expressed in fat and striated muscle tissues. 2 In these tissues, the majority of GLUT4 molecules (Ϸ90%) are sequestered in intracellular vesicles in the absence of insulin or other stimuli such as muscle contraction. 3,4 In the presence of these stimuli, the GLUT4-containing vesicles translocate to the plasma membrane where they participate in glucose uptake.Vascular smooth muscle has been shown to express GLUT1 5 as well as GLUT4. 6 -10 However, the expression of other facilitative glucose transporters in vascular smooth muscle is unknown. Previous studies from our laboratory have demonstrated that in vascular diseases caused by ...

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Section: Discussionmentioning

confidence: 89%

“…Angiotensin (Ang) II-mediated hypertension was induced in wildtype male C57BL/6J mice (12 to 14 weeks old) (Jackson Laboratories, Bar Harbor, Maine) as previously described [22][23][24] and outlined in detail in the online supplement.…”

Section: Mouse Model Of Angiotensin Ii-mediated Hypertensionmentioning

confidence: 99%

GLUT4 Facilitative Glucose Transporter Specifically and Differentially Contributes to Agonist-Induced Vascular Reactivity in Mouse Aorta

Park

Loberg

Duquaine

et al. 2005

ATVB

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“…Recently, the expression of NADPH oxidase subunits (p22phox, p67phox, gp91phox, etc.) has been shown to be upregulated in several tissues in cardiovascular diseases (32,(47)(48)(49). In diabetic rats, renal expression of p47phox, when evaluated by Western blot analysis and immunohistochemistry, has been shown to be increased in the kidney (5).…”

Section: Discussionmentioning

confidence: 99%

Translocation of Glomerular p47phox and p67phox by Protein Kinase C-β Activation Is Required for Oxidative Stress in Diabetic Nephropathy

et al. 2003

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Oxidative stress is implicated to play an important role in the development of diabetic vascular complications, including diabetic nephropathy. It is unclear whether oxidative stress is primarily enhanced in the diabetic glomeruli or whether it is merely a consequence of diabetes-induced glomerular injury. To address this issue, we examined diabetic glomeruli to determine whether oxidative stress is enhanced, as well as examined the role of protein kinase C (PKC)-␤ activation in modulating NADPH oxidase activity. Urinary 8-hydroxydeoxyguanosine excretion and its intense immune-reactive staining in the glomeruli were markedly higher in diabetic than in control rats, and these alterations were ameliorated by a treatment with a selective PKC-␤ inhibitor, ruboxistaurin (RBX; LY333531) mesylate, without affecting glycemia. NADPH oxidase activity, which was significantly enhanced in diabetic glomeruli and the source of reactive oxygen species (ROS) generation, was also improved by RBX treatment by preventing the membranous translocation of p47phox and p67phox from cytoplasmic fraction without affecting their protein levels. Adenoviral-mediated PKC-␤ 2 overexpression enhanced ROS generation by modulating the membranous translocation of p47phox and p67phox in cultured mesangial cells. We now demonstrate that oxidative stress is primarily enhanced in the diabetic glomeruli due to a PKC-␤-dependent activation of NADPH oxidase resulting in ROS generation.

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“…Recent studies (5) suggest that a significant source of intracellular ROS in cardiovascular cells is a phagocyte-type NADPH oxidase. AngII activates NADPH oxidases in vascular smooth muscle (5,6), fibroblasts (7), endothelial cells (EC) (8,9), and cardiomyocytes (10). Furthermore, NADPH oxidase activation and increased ROS production are implicated in AngII-stimulated vascular smooth muscle hypertrophy (3,5) and in AngII-dependent hypertension and the associated endothelial dysfunction (11)(12)(13).…”

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confidence: 99%