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Abstract

Nitric oxide degradation linked to endothelial dysfunction plays a central role in cardiovascular diseases. Superoxide producing enzymes such as NADPH oxidase and xanthine oxidase are responsible for NO degradation as they generate a variety of reactive oxygen species (ROS). Moreover, superoxide is rapidly degraded by superoxide dismutase to produce hydrogen peroxide leading to the uncoupling of NO synthase and production of increased amount of superoxide. Angiotensin II is an important stimulus of NADPH oxidase. Through its AT(1) receptor, Ang II stimulates the long-term increase of several membrane component of NADPH oxidase such as P(22) phox or nox-1 and causes an increased activity of NADPH oxidase with inactivation of NO leading to impaired endothelium-dependent vasorelaxation, vascular smooth muscle cell hypertrophy, proliferation and migration, extracellular matrix formation, thrombosis, cellular infiltration and inflammatory reaction. Several preclinical and clinical studies have now confirmed the involvement of the AT(1) receptor in endothelial dysfunction. It is proposed that the AT(2) receptor counterbalances the deleterious effect of the Ang II-induced AT(1) receptor stimulation through bradykinin and NOS stimulation. This mechanism could be especially relevant in pathological cases when the NADPH oxidase activity is blocked with an AT(1) receptor antagonist.

Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis

“…The consumption of a large amount of NAPDH was caused by inflammation in the patients with SAP. Inhibition of superoxide and ROS generation resulted in suppression of NO production, exacerbating local microcirculation disturbances [ 42 43 ]. Then, leukocyte adhesion increased due to local microcirculatory hemodynamic changes [ 42 43 ].…”

Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

“…Local inflammation can enhance the ability of angiotensin II to induce vascular remodeling [274]. Typically, angiotensin II stimulates expression of PDGF and TGF-β through activation of AT 1 receptors [275], and can increase eNOS and NO release in fetoplacental artery endothelial cells [276]. Angiotensin II can also transactivate certain tyrosine kinase receptors, including those that mediate responses to PDGF [262, 277].…”

“…These ROS molecules, which may originate from membrane-bound NADPH oxidase or mitochondrial synthesis [279], can induce vascular smooth muscle hypertrophy, hyperplasia, and migration [280, 281]. Activation of AT 1 by angiotensin II can increase the expression and activity of membrane-bound NADPH oxidase, and thereby stimulate ROS production [275, 278]. Increases in ROS can, in turn, have many effects including reaction with NO leading to decreased NO bioavailability.…”

Effect of hypertension and its reverse on serum nitric oxide concentration and vascular permeability in two-kidney one-clip hypertensive rats

“…Decreased NO bioavailability in hypertensive subjects may results from lower NO production such as deficiency in L-arginine/BH4 (Cosentino and Luscher 1999;Zhou et al 2001) or increased NO degradation due to higher superoxide anion generation or reduced level of antioxidant (Schulman et al 2005). Furthermore, 2K1C goldblatt model induces renin-angiotensin dependent hypertension and another explanation for reduced NO availability in this model of hypertension is that high angiotensin II level decreases NO bioavailability by promoting oxidative stress (de Gasparo 2002).…”