Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Abstract

Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

Immune Mechanisms in Arterial Hypertension

“…The NADPH oxidases have evolved to have numerous roles in other cells, including modulation of sympathetic outflow, vascular tone, and renal sodium reabsorption, all of which contribute to hypertension. 14,15 The sympathetic nervous system and hypothalamic pituitary axis are two major pathways in which the NADPH oxidases modulate neuroimmune communication. The sympathetic nervous system innervates both primary (thymus, bone marrow) and secondary tissues and lymphoid tissues (spleen, lymph nodes), and most immune cells express receptors for neurohormones and catecholamines.…”

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

“…ERS is a key player in endothelial dysfunction during hypertension [118] . Reactive oxygen species (ROS) overproduction or the increase of oxidative stress impaired endothelial function in hypertension [119] . ERS may induce oxidative stress to impair endothelial function in the development of hypertension.…”

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

“…In phagocytic cells, ROS play a role in host‐defense responses, and in nonphagocytic cells, ROS control cell differentiation, proliferation, apoptosis, and senescence 1, 2. In the vascular system, ROS regulate vasculogenesis, endothelial function, and vascular tone 3, 4. In cardiovascular diseases, such as hypertension,5 atherosclerosis,6 and pulmonary arterial hypertension,7 Nox‐derived ROS generation is increased, leading to endothelial dysfunction and vascular injury.…”