Jessica R C Priestley1, Katie E Fink1, Joe M McCord2, Julian H Lombard1. 1. Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin. 2. Division of Pulmonary Sciences and Critical Care Medicine Research, University of Colorado at Denver - Anschutz Medical Campus, Aurora, Colorado.
Abstract
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.
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.
Authors: Jessica R C Priestley; Katie E Kautenburg; Marc C Casati; Bradley T Endres; Aron M Geurts; Julian H Lombard Journal: Am J Physiol Heart Circ Physiol Date: 2015-12-04 Impact factor: 4.733
Authors: Estefania Toledo; Frank B Hu; Ramon Estruch; Pilar Buil-Cosiales; Dolores Corella; Jordi Salas-Salvadó; M Isabel Covas; Fernando Arós; Enrique Gómez-Gracia; Miquel Fiol; Jose Lapetra; Luis Serra-Majem; Xavier Pinto; Rosa M Lamuela-Raventós; Guillermo Saez; Mònica Bulló; Valentina Ruiz-Gutiérrez; Emilio Ros; José V Sorli; Miguel Angel Martinez-Gonzalez Journal: BMC Med Date: 2013-09-19 Impact factor: 8.775