Send to

Choose Destination
Microcirculation. 2019 May 27:e12575. doi: 10.1111/micc.12575. [Epub ahead of print]

NRF2 activation with Protandim attenuates salt-induced vascular dysfunction and microvascular rarefaction.

Author information

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Division of Pulmonary Sciences and Critical Care Medicine Research, University of Colorado at Denver - Anschutz Medical Campus, Aurora, Colorado.



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.


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.


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.


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.


NRF2; Protandim; antioxidants; cerebral circulation; endothelial dysfunction; oxidant stress; reactive oxygen species; resistance arteries; salt; sodium; superoxide dismutase; vascular dysfunction; vasodilation


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center