Consistent antioxidant and antihypertensive effects of oral sodium nitrite in DOCA-salt hypertension

Abstract

Hypertension is a common disease that includes oxidative stress as a major feature, and oxidative stress impairs physiological nitric oxide (NO) activity promoting cardiovascular pathophysiological mechanisms. While inorganic nitrite and nitrate are now recognized as relevant sources of NO after their bioactivation by enzymatic and non-enzymatic pathways, thus lowering blood pressure, mounting evidence suggests that sodium nitrite also exerts antioxidant effects. Here we show for the first time that sodium nitrite exerts consistent systemic and vascular antioxidant and antihypertensive effects in the deoxycorticosterone-salt (DOCA-salt) hypertension model. This is particularly important because increased oxidative stress plays a major role in the DOCA-salt hypertension model, which is less dependent on activation of the renin-angiotensin system than other hypertension models. Indeed, antihypertensive effects of oral nitrite were associated with increased plasma nitrite and nitrate concentrations, and completely blunted hypertension-induced increases in plasma 8-isoprostane and lipid peroxide levels, in vascular reactive oxygen species, in vascular NADPH oxidase activity, and in vascular xanthine oxidoreductase activity. Together, these findings provide evidence that the oral administration of sodium nitrite consistently decreases the blood pressure in association with major antioxidant effects in experimental hypertension.

Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite

“…A variety of factors could affect the Km or velocity of XOR-mediated reactions using nitrite as a substrate, such as absence of oxygen [35], excess of NADH [36], absence of xanthine [36], and the activity of other enzymes that could scavenge reactive oxygen species [36]. Moreover, the concentration of XOR we utilized was probably in excess as compared with those found in rats [11], [37]. Therefore, the extent of nitrate-induced inhibition or XOR-mediated nitrite reductase activity in the tissues could be significantly different from that found in in vitro studies.…”

Therapeutic value of stimulating the nitrate‐nitrite‐nitric oxide pathway to attenuate oxidative stress and restore nitric oxide bioavailability in cardiorenal disease

“…UNX–HS), comparable favourable effects were noted following L‐arginine and tempol treatments that also restored balance between ROS and NO , and by unilateral renal denervation that reduces sympathetic nerve activity . Studies conducted by another group showed that treatment with inorganic nitrite lowered oxidative stress and blood pressure dose‐dependently in two different rat models of renovascular hypertension, that is two‐kidney one‐clip (2K1C) and deoxycorticosterone (DOCA)–salt treatment .…”

Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension

“…For example, beetroot due to its high inorganic nitrate content is considered as an adjuvant for the treatment of hypertension [32, 33]. In different animal models of hypertension, treatment with nitrate and/or nitrite, which boost NO levels, is effective in reducing elevated blood pressure [34–37]. In addition, acute and short-term hypotensive effects of inorganic nitrates have been reported in several clinical studies [38–41] as well as in meta-analyses [42, 43].…”