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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Heart+Circ+Physiol
2015 ; 309
(5
): H926-34
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?-Lipoic acid reduces neurogenic hypertension by blunting oxidative
stress-mediated increase in ADAM17
#MMPMID26254330
de Queiroz TM
; Xia H
; Filipeanu CM
; Braga VA
; Lazartigues E
Am J Physiol Heart Circ Physiol
2015[Sep]; 309
(5
): H926-34
PMID26254330
show ga
We previously reported that type 2 angiotensin-converting enzyme (ACE2)
compensatory activity is impaired by the disintegrin and metalloprotease 17
(ADAM17), and lack of ACE2 is associated with oxidative stress in neurogenic
hypertension. To investigate the relationship between ADAM17 and oxidative
stress, Neuro2A cells were treated with ANG II (100 nM) 24 h after vehicle or
?-lipoic acid (LA, 500 ?M). ADAM17 expression was increased by ANG II (120.5 ±
9.1 vs. 100.2 ± 0.8%, P < 0.05) and decreased after LA (69.0 ± 0.3 vs. 120.5 ±
9.1%, P < 0.05). In another set of experiments, LA reduced ADAM17 (92.9 ± 5.3 vs.
100.0 ± 11.2%, P < 0.05) following its overexpression. Moreover, ADAM17 activity
was reduced by LA in ADAM17-overexpressing cells [109.5 ± 19.8 vs. 158.0 ± 20.0
fluorescence units (FU)·min(-1)·?g protein(-1), P < 0.05], in which ADAM17
overexpression increased oxidative stress (114.1 ± 2.5 vs. 101.0 ± 1.0%, P <
0.05). Conversely, LA-treated cells attenuated ADAM17 overexpression-induced
oxidative stress (76.0 ± 9.1 vs. 114.1 ± 2.5%, P < 0.05). In deoxycorticosterone
acetate (DOCA)-salt hypertensive mice, a model in which ADAM17 expression and
activity are increased, hypertension was blunted by pretreatment with LA (119.0 ±
2.4 vs. 131.4 ± 2.2 mmHg, P < 0.05). In addition, LA improved dysautonomia and
baroreflex sensitivity. Furthermore, LA blunted the increase in NADPH oxidase
subunit expression, as well as the increase in ADAM17 and decrease in ACE2
activity in the hypothalamus of DOCA-salt hypertensive mice. Taken together,
these data suggest that LA might preserve ACE2 compensatory activity by breaking
the feedforward cycle between ADAM17 and oxidative stress, resulting in a
reduction of neurogenic hypertension.
|*Oxidative Stress
[MESH]
|ADAM Proteins/genetics/*metabolism
[MESH]
|ADAM17 Protein
[MESH]
|Angiotensin II/pharmacology
[MESH]
|Angiotensin-Converting Enzyme 2
[MESH]
|Animals
[MESH]
|Antioxidants/*pharmacology/therapeutic use
[MESH]