Oxidative stress causes hypertension and activation of nuclear factor-κB after high-fructose and salt treatments

Abstract

There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks. Fructose-fed rats exhibited a salt-dependent hypertension accompanied by decrease in renal superoxide dismutase activity, which is the first footprint of antioxidant inactivation by reactive oxygen species (ROS). Metabolic changes and the hypertensive effect of the combined fructose-salt diet (20 weeks) were markedly reversed by a superoxide scavenger, Tempol (10 mg/kg, gavage); moreover, Tempol (50 mM) potentially reduced ROS production and abolished nuclear factor-kappa B (NF-κB) activation in human embryonic kidney HEK293 cells incubated with L-fructose (30 mM) and NaCl (500 mosmol/kg added). Taken together, our data suggested a possible role of oxygen radicals and ROS-induced activation of NF-κB in the fructose- and salt-induced hypertension associated with the progression of the renal disease.

Imoxin attenuates high fructose‐induced oxidative stress and apoptosis in renal epithelial cells via downregulation of protein kinase R pathway

“…Interestingly, significant reduction in inflammatory and apoptotic markers has also been observed in HF‐treated cultured renal epithelial cells co‐incubated with imoxin (C16) ( Figure ). High fructose is often linked with oxidative stress , and in the present study, we have demonstrated that HF increases ROS generation in renal epithelial cells via activation of PKR pathway.…”

Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2receptor deficient mice

“…Consistent with the role of PGI 2 in restraining oxidative stress in atherosclerotic vasculature (18) and in salt-induced hypertension (19,20) and the elevation of PGI 2 biosynthesis on the HSD (Figure 2), excretion of a major urinary F 2 -isoprostane (F 2 iP), an index of lipid peroxidation, was not significantly elevated in Ldlr KOs after 2 weeks on a HSD ( Figure 4C and 4D). However, rather than increase with Ipr deletion, F 2 iP excretion, just like BP, unexpectedly fell, consistent with the changes in mitochondrial dysfunction and oxidative phosphorylation genes observed in the renal medulla of Ipr/Ldlr DKO mice (mostly downregulated in the Ipr/Ldlr DKO) ( Figure 4D).…”

Antihypertensive Effect of Polyphenol-Rich Fraction of Azadirachta indica on Nω-Nitro-L-Arginine Methyl Ester-Induced Hypertension and Cardiorenal Dysfunction

“…The immunohistochemistry of cardiac and renal tissue revealed higher NF-kB expressions in L-NAME-induced hypertensive rats relative to the control and rats co-treated with AI and captopril. The activation of NF-kB by oxidative stress has been associated with ventricular remodeling and arterial hypertension [60,61]. This was suggestive of the involvement of NF-kB signaling in cardiorenal dysfunction following L-NAME-induced hypertension.…”