NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis

Abstract

Citation:Santillo M, Colantuoni A , Mondola P, Guida B and Damiano S (2015) NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis. Front. Physiol. 6:194. doi: 10.3389/fphys.2015.00194 NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis Mariarosaria Santillo *, Antonio Colantuoni, Paolo Mondola, Bruna Guida and Simona DamianoDipartimento di Medicina Clinica e Chirurgia, Università di Napoli "Federico II," Naples, ItalyBlood pressure homeostasis is maintained by several mechanisms regulating cardiac output, vascular resistances, and blood volume. At cellular levels, reactive oxygen species (ROS) signaling is involved in multiple molecular mechanisms controlling blood pressure. Among ROS producing systems, NADPH oxidases (NOXs), expressed in different cells of the cardiovascular system, are the most important enzymes clearly linked to the development of hypertension. NOXs exert a central role in cardiac mechanosensing, endothelium-dependent relaxation, and Angiotensin-II (Ang-II) redox signaling regulating vascular tone. The central role of NOXs in redox-dependent cardiovascular cell functions renders these enzymes a promising pharmacological target for the treatment of cardiovascular diseases, including hypertension. The aim of the present review is to focus on the physiological role of the cardiovascular NOX-generating ROS in the molecular and cellular mechanisms affecting blood pressure.Keywords: NOX, blood pressure, reactive oxygen species, redox signaling, cardiomyocytes, endothelial cells, vascular smooth muscle cells, Ang II signaling Blood Pressure RegulationBlood pressure is regulated by a dynamic equilibrium of different complex mechanisms (Opie, 2004;Raven and Chapleau, 2014). The main factor determining the systemic blood pressure is the blood arterial volume that, in turn, depends on the cardiac output and vascular resistances. In addition to the nervous and chemical factors, the cardiac output, is affected by mechanical factors ensuring the adjustment of cardiac output to the venous return and afterload. On the other hand, vascular resistance depends in part on the characteristics of the blood (viscosity) and on the diameter of the vascular lumen. Smooth muscle cell layer of the resistance arteries may contract or relax resulting in a parallel increase or decrease of blood pressure, respectively. Several mechanisms regulate vascular tone. Adrenergic sympathetic fibers exert a vasoconstrictory effect through the activation of alfa1-adrenergic receptors of the vascular smooth muscle cells (VSMCs). In addition, paracrine, hormonal and mechanical mechanisms contribute to the fine regulation of vascular tone modulating blood pressure.

The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme

“…The SOD1 is ubiquitous in mammalian cells and is expressed at relatively high levels also in blood vessels; in normal mouse aorta the activity of SOD1 accounts for 50–80% of total SOD activity; a similar pattern of expression was observed in human arteries (Horiuchi et al, 2004; Santillo et al, 2015). In physiological conditions, the superoxide dismutases, together with the non-enzymatic ROS scavengers as vitamins E, A, and C maintain a steady state between oxidant and antioxidant systems (Russo et al, 2011).…”

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

“…As mentioned in an earlier section, ROS production via NADPH oxidase, Nox, induced by ANG II has been strongly implicated in ANG II pathophysiology, including enhanced vasoconstriction, endothelial dysfunction, vascular remodeling, and hypertension. There are excellent reviews focusing on the signaling and cellular mechanisms of this topic (308,537,711,746,911). The readers is suggested to refer to these articles for molecular understanding of ROS regulation in the vasculature.…”

Enhanced XOR activity in eNOS-deficient mice

“…AngII acts on two different receptor types called AT 1 and AT 2 . Activation of AT 1 has been linked to higher NOX mediated ROS production, induction of vasoconstriction and therefore possible detrimental effects in the cardiovascular system, whereas the opposite function has been suggested for the AT 2 receptor [151]. Moreover, elevated NOX activity can lead to transcriptional upregulation of the AT 1 receptor whereby a vicious cycle is created [152].…”