NRF2 activation with Protandim attenuates salt-induced vascular dysfunction and microvascular rarefaction.
HYPOTHESIS
This study tested the hypothesis that dietary activation of the master antioxidant and cell protective transcription factor nuclear factor, erythroid -2-like 2 (NRF2), protects against salt-induced vascular dysfunction by restoring redox homeostasis in the vasculature.


METHODS
Male Sprague-Dawley rats and Syrian hamsters were fed a HS (4.0% NaCl) diet containing ~60 mg/kg/day Protandim supplement for 2 weeks and compared to controls fed HS diet alone.


RESULTS
Protandim supplementation restoredendothelium-dependent vasodilation in response to acetylcholine (ACh) in middle cerebral arteries (MCA)of HS-fed rats and hamster cheek pouch arterioles, and increased microvessel density in the cremastermuscle of HS-fed rats. The restored dilation to ACh in MCA of Protandim-treated rats was prevented by inhibiting nitric oxide synthase (NOS) with L-NAME [100 μM] and was absent in MCA from Nrf2(-/-) knockout rats fed HS diet. Basilar arteries from HS-fed rats treated with Protandim exhibited significantly lower staining for mitochondrial oxidizing species than untreated animals fed HS diet alone; and Protandim treatment increased MnSOD (SOD2) protein expression in mesenteric arteries of HS-fed rats.


CONCLUSIONS
These results suggest that dietary activation of NRF2 protects against salt-induced vascular dysfunction, vascular oxidative stress, and microvascular rarefaction by upregulating antioxidant defenses and reducing mitochondrial ROS levels.
['Priestley|Jessica R C|JRC|', 'Fink|Katie E|KE|', 'McCord|Joe M|JM|', 'Lombard|Julian H|JH|0000-0002-6920-4736']
D000818:Animals D001160:Arterioles D004365:Drugs, Chinese Herbal D018507:Gene Expression Regulation, Developmental D008297:Male D008638:Mesenteric Arteries D008647:Mesocricetus D008833:Microcirculation D020768:Middle Cerebral Artery D051267:NF-E2-Related Factor 2 D051381:Rats D017207:Rats, Sprague-Dawley D017673:Sodium Chloride, Dietary D013482:Superoxide Dismutase D014652:Vascular Diseases D014664:Vasodilation
NRF2 Protandim vascular dysfunction antioxidants vasodilation oxidant stress cerebral circulation endothelial dysfunction reactive oxygen species resistance arteries salt sodium superoxide dismutase