Abstract-The atherogenic effect of the renin-angiotensin system can be explained, in part, by the influence of its effector, angiotensin II (Ang II), on vascular smooth muscle cell (VSMC) growth. There is evidence that reactive oxygen species (ROS) play a role in the atherogenesis and activation of mitogen-activating protein (MAP) kinases, which are involved in proliferation and differentiation. The study was performed to further characterize the role of ROS in Ang II-mediated MAP kinase activation and the regulation of the transcription factor activator protein-1 (AP-1). Rat VSMCs were stimulated with Ang II. The activities of MAP kinases were assessed by Western blot analysis or by immunocomplex kinase assay. AP-1 binding was determined by using an electrophoretic mobility shift assay. Rat VSMCs were treated with Ang II-activated MAP kinases, extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK), p38 MAP kinase (p38 MAPK), and their downstream effector, AP-1. Interestingly, only the activation of ERK1/2, but not JNK or p38 MAPK, was tyrosine kinase, protein kinase C, and MEK1/2 dependent. Ang II also induced the rapid formation of ROS, which could be inhibited by a specific antibody as well as by antisense against the p22phox subunit of the NAD(P)H oxidase. JNK and p38 MAPK, but not ERK, activation was inhibited by an inhibitor of NAD(P)H oxidase. Antisense against p22phox also solely inhibited p38 MAPK but did not affect ERK. The results indicate that in VSMCs, Ang II activates MAP kinases and AP-1 through different pathways; the results further suggest that ROS, generated by p22phox, mediate Ang II-induced JNK and p38 MAPK activation, which may contribute to the pathogenesis of atherosclerosis. Key Words: angiotensin II Ⅲ atherosclerosis Ⅲ reactive oxygen species Ⅲ mitogen-activated protein kinase Ⅲ activator protein-1 A ngiotensin II (Ang II), the main peptide hormone of the renin-angiotensin system, plays an important role in the pathogenesis of cardiovascular diseases, including atherosclerosis, myocardial infarction, and hypertension. 1 Ang II exerts hypertrophic and hyperplastic effects by activating a number of intracellular signal transduction pathways through a 7-transmembrane heterotrimeric G protein-coupled receptor called the Ang II type 1 (AT 1 ) receptor. 2 New data indicate that Ang II plays an important role in the generation of reactive oxygen species (ROS) by activation of NAD(P)H oxidase, a plasma membrane-bound protein. 3,4

Patients with sclerosing cholangitis, following septic shock, represent a new variant of vanishing bile duct disorders. In such patients liver disease rapidly progresses to cirrhosis. Endoscopic treatment may only transiently improve the course of the disease. Orthotopic liver transplantation is indicated in end stage disease.

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Beside nonsteroidal anti-inflammatory steroid drug use, antihypertensive medication and concomitant arteriosclerotic diseases are risk factors for colonic diverticular hemorrhage. Our results support the hypothesis of an altered arteriosclerotic vessel as the source of bleeding.

In decompensated cirrhosis procalcitonin serum levels provided the most sensitive and specific tool for the initial diagnosis of bacterial infection.