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A role for Nrf2 in the prevention of salt‐induced vascular dysfunction
Author(s) -
Priestley Jessica R. C.,
Dahlgren Allison F.,
Weinberg Brian D.,
McCord Joe M.,
Lombard Julian H.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1189.11
Subject(s) - endocrinology , medicine , chemistry , oxidative stress , angiotensin ii , acetylcholine , mesenteric arteries , keap1 , antioxidant , transcription factor , biochemistry , gene , blood pressure , artery
Consumption of a high salt (HS) diet results in vascular oxidant stress and impairs endothelium‐dependent relaxation in a variety of human and experimental models. Nuclear factor erythroid‐2‐related factor 2 (Nrf2) is a transcription factor that induces the expression of many critical antioxidant genes. We measured protein expression of Nrf2 and its cytosolic inhibitor, kelch‐like ECH‐associated protein 1 (Keap1), in mesenteric and cerebral arterial homogenates from Sprague‐Dawley (SD) rats fed HS (4% NaCl), low salt (LS), or HS with low dose angiotensin II (ANG II) infusion to restore normal plasma ANG II levels. While Nrf2 expression was similar between groups, Keap1 expression was significantly lower in ANG II‐infused rats (p < 0.05). The Nrf2:Keap1 ratio normalized to LS was significantly increased in both mesenteric (LS = 100.00% ± 19.76; HS = 176.34% ± 29.98; HS + ANG II = 561.44% ± 210.39) and cerebral (LS = 100.00% ± 16.21; HS = 181.67% ± 69.31; HS + ANG II = 677.55% ± 172.38) arterial beds. The dietary supplement Protandim, shown to induce Nrf2 expression, improved endothelium‐dependent relaxation to acetylcholine in salt‐fed SD rats (HS = 0.50 μm ± 0.96; HS + Protandim = 6.67 μm ± 1.28; p = 0.008) and hamsters (HS = 1.33 μm ± 0.52; HS + Protandim = 5.60 μm ± 0.68; p < 0.001 ). Together, these data suggest a functional role for the Nrf2 antioxidant defense system in preventing salt‐induced vascular dysfunction.