Atherosclerosis is the primary cause of heart disease. A risk factor of atherosclerosis is the increased generation of superoxide anions (⋅O2−). The NAD(P)H oxidase is the main source of the endothelial (⋅O2−) generation. This enzyme consists of four subunits: gp91phox, p22phox, p47phox and p67phox. Furthermore, Nox4 was identified as a novel homolog of the catalytic subunit gp91phox in human umbilical vene endothelial cells (HUVEC). However, the structure and function of the complex is not well understood in endothelial cells. In this work, the influence of proatherosclerotic endothelin-1 (ET-1) on regulation of different NAD(P)H oxidase subunits including Nox4 was analysed. The mRNA expression was quantified by standard calibrated competitive RT-PCR. ET-1 induced gp91phox mRNA expression after by an ET-1 receptor type B (ETB)-mediated pathway. The induction of gp91phox coincided with an increased generation as quantified by coelenteracine-mediated chemiluminescence. The generated oxidates low-density lipoprotein (LDL) to oxLDL. The oxLDL is taken up by the lectin-like oxLDL receptor LOX-1. Therefore, in further studies the effect of ET-1 on expression of LOX-1 was investigated. ET-1 induced the expression of LOX-1. The oxLDL uptake of HUVEC was quantified by fluorescence-labeled oxLDL. ET-1 stimulated oxLDL uptake via ETB. Angiotensin II (Ang II) also augmented NAD(P)H oxidase expression and (⋅O2−) generation in HUVEC. Ang II induced LOX-1 expression as well. On the basis of this increased (⋅O2−) generation and oxLDL uptake, ET-1 and Ang II could promote endothelial dysfunction and development of atherosclerosis. Arterial laminar shear stress is known as an antiatherosclerotic stimulus. Laminar shear stress inhibits the release of ET-1 and the expression of angiotensin converting enzyme (ACE) and induces the release of vasoprotective nitric oxide (NO). In further studies, the effect of laminar shear stress on regulation of NAD(P)H oxidase was investigated. Arterial laminar shear stress downregulated the expression of gp91phox, Nox4 and p47phox. This downregulation was mediated by ETB receptor and angiotensin receptor type 1 (AT1). The mRNA expression of gp91phox, but not of Nox4, was regulated by NO. The application of arterial laminar shear stress inhibited generation as measured by cytochrom c assay by an NO-mediated mechanism. These data suggest, that the catalytic subunit gp91phox could have an higher impact on endothelial (⋅O2−) generation than its homolog Nox4. Arterial laminar shear stress reduced the oxLDL uptake in endothelial cells, too. This new mechanism might contribute to the vasoprotective properties of arterial laminar shear stress. A standard therapy of hypertension and heart failure is the treatment with ACE inhibitors. In clinical studies, the influence of ACE inhibitor therapy on expression of NAD(P)H oxidase subunits in the left ventricle of patients with heart failure was investigated. Protein expression of gp91phox, Nox4, p47phox and p67phox was downregulated by ACE inhibitor treatment. Because the antioxidative capacity of human myocardium we were not able to measure (⋅O2−) generation in these tissues. Nevertheless these data suggest an antioxidative potential of ACE inhibitor therapy.