Oxidative Stress and Hypertension

Abstract

A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modify complex signaling pathways to promote hypertension has expanded significantly. In this review, we summarize recent advances in delineating the primary and secondary sources of reactive oxygen species (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, endoplasmic reticulum, and mitochondria), the posttranslational oxidative modifications they induce on protein targets important for redox signaling, their interplay with endogenous antioxidant systems, and the role of inflammasome activation and endoplasmic reticular stress in the development of hypertension. We highlight how oxidative stress in different organ systems contributes to hypertension, describe new animal models that have clarified the importance of specific proteins, and discuss clinical studies that shed light on how these processes and pathways are altered in human hypertension. Finally, we focus on the promise of redox proteomics and systems biology to help us fully understand the relationship between ROS and hypertension and their potential for designing and evaluating novel antihypertensive therapies.

Paternal long-term PM2.5 exposure causes hypertension via increased renal AT1R expression and function in male offspring

“…In our present study, we found that compared with the offspring of vehicle-treated paternal rats, the expression and anti-natriuretic function of renal AT 1 R were aggravated in the offspring of PM 2.5 -exposed paternal rats, which was accompanied by increased expression of its upstream GRK4 [22,40]. Further study showed increased oxidative stress, one of the fundamental mechanisms responsible for the development of hypertension [41,42], in paternal rats may be involved in it because administration with an antioxidant tempol for 16 weeks in paternal PM 2.5 -treated rats restored the increased SBP and impaired sodium excretion, reversed the increased renal AT 1 R and GRK4 expression in offspring.…”

Amelioration of endothelial dysfunction by sodium glucose co-transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection

“…Oxidative stress causes endothelial nitric oxide synthase (eNOS) uncoupling and impairs NO production, the key vasodilator. ROS produced by NOXs also oxidize the sarcoendoplasmic reticulum calcium transport ATPase and limit the sensitivity of SMC to NO (Griendling et al , 2021). Besides, ROS induce vascular stiffness via upregulating the expression of vasoactive factors like vascular endothelial growth factor (VEGF) and extracellular proteins like matrix metalloproteinases (Griendling et al , 2021).…”

“…ROS produced by NOXs also oxidize the sarcoendoplasmic reticulum calcium transport ATPase and limit the sensitivity of SMC to NO (Griendling et al , 2021). Besides, ROS induce vascular stiffness via upregulating the expression of vasoactive factors like vascular endothelial growth factor (VEGF) and extracellular proteins like matrix metalloproteinases (Griendling et al , 2021). Vascular remodeling elevates blood pressure and increases the intensity of cyclic stretch caused by vasoconstriction-dilation circles (Ohishi, 2018).…”

Nano-Drug Design Based on the Physiological Properties of Glutathione

“…A large amount of sorbitol accumulation results in excessive sorbitol in the cell and damages the cell permeability owing to their low lipophilicity. Subsequently, sorbitol does not penetrate the cell membrane, and further cause cell swelling and rupture, inducing a series of diabetes and chronic complications development [34][35][36][37]. GSSH can deplete NADPH and be reduced to GSH by GSH-R.…”