Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction.

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo.

Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo.

Objective: Increased reactive oxygen species (ROS) production is involved in the pathophysiology of endothelial dysfunction. NADPH oxidase-4 (Nox4) is a ROS-generating enzyme expressed in the endothelium, levels of which increase in pathological settings. Recent studies indicate that it generates predominantly hydrogen peroxide (H(2)O(2)), but its role in vivo remains unclear.

Reactive oxygen species and endothelial activation.

Endothelial activation refers to a specific change in endothelial phenotype, characterized most notably by an increase in endothelial-leukocyte interactions and permeability, which is pivotal to inflammatory responses in both physiologic and pathologic settings. An increasing body of evidence indicates an important role for reactive oxygen species (ROS)-mediated modulation of signal-transduction pathways in many of the processes involved in endothelial activation. ROS generated by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes may be especially important in this regard.

NADPH oxidase-derived reactive oxygen species in the regulation of endothelial phenotype.

Endothelial dysfunction comprising impairment of endothelium-dependent vasodilator function and increased endothelial activation contributes to the pathophysiology of cardiovascular diseases such as atherosclerosis, diabetic vasculopathy, heart failure and hypertension. The changes in endothelial phenotype in these conditions occur in response to diverse stimuli including inflammatory cytokines, activation of renin-angiotensin-aldosterone system, hyperlipidaemia, hyperglycemia, ischemia-reperfusion and mechanical forces. An increased production of reactive oxygen species (ROS), such as superoxide and H(2)O(2) is involved in the genesis of these alterations in endothelial phenotype.

Poloxamer 407 (P-407)-mediated reduction in the gene expression of ATP-binding-cassette transporter A1 may contribute to increased cholesterol in peripheral tissues of P-407-treated rats.

The purpose of this study was to determine whether poloxamer 407, a chemical known to increase plasma lipid levels in rodents following parenteral administration, decreased the gene expression of ATP-binding-cassette transporter A1. Using human macrophages cultured with poloxamer 407, there was a significant reduction in the gene expression of ATP-binding-cassette transporter A1; however, there was no effect on the gene expression of either fatty acid synthase or sterol regulatory element binding protein-1. Reduction of ATP-binding-cassette transporter A1 mRNA levels was also observed in both liver and intestine of poloxamer 407-treated rats.