Low dose dietary nitrate improves endothelial dysfunction & plaque stability in the ApoE-/- mouse fed a high fat diet

Mechanisms underlying blood pressure reduction by dietary inorganic nitrate

“…However, a study using low‐density lipoprotein receptor knockout mice fed with a western diet for 14 weeks concluded that dietary nitrate supplementation did not affect blood pressure, systemic and tissue immune cells or atherosclerosis development . In contrast, subsequent studies conducted by independent laboratories showed that long‐term nitrate supplementation improved endothelial dysfunction and plaque stability in ApoE knockout mice fed a high‐fat diet for approximately 10 weeks . The latter study supports previous findings regarding reduced leucocyte rolling and adherence, but also show that dietary nitrate supplementation reduced number of circulating neutrophils, and attenuated monocyte activation through direct repression of neutrophil activation and upregulation of IL‐10‐dependent anti‐inflammatory pathways in atheroprone mice.…”

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

“…Intriguingly, in this study, we showed that tissues of the ApoE KO expressed greater nitrite reductase activity assessed ex vivo and that this activity, at least in part, was driven by elevated XOR activity, observations fitting with studies in humans indicating that individuals with coronary artery disease have increased vascular XOR expression and activity (Spiekermann et al, 2003). In a separate study, low to moderate dosing with KNO 3 (0.1 and 1 mmol/kg per day) but not high-dose (10 mmol/kg per day) supplementation for 10 weeks in ApoE KO mice was associated with increased collagen expression and reduced lipid deposition and also, similarly, no differences in plaque size (Bakker et al, 2016). These two latter studies support the contention that reduced inflammation within the atherosclerotic plaques coupled with increased smooth muscle and collagen content, although not influencing plaque size, likely provides a more stable plaque phenotype (Stefanadis et al, 2017).…”

“…Long-term dietary nitrite and nitrate deficiency worsens ex vivo-assessed endothelial function in C57BL6 mice and was associated with CV death (Kina-Tanada et al, 2017). Additionally, nitrite supplementation improves ex vivo endothelial function in several different models associated with cardiometabolic disease (Sindler et al, 2015;Ling et al, 2016), whereas dietary nitrate has been shown to improve endothelial function in models of atherosclerosis (Bakker et al, 2016) as well as to prevent the endothelial dysfunction that occurs in mice subjected to long-term low dietary nitrate and nitrite (Kina-Tanada et al, 2017) or aging (Rammos et al, 2015).…”