The roles of ERK1/2 and PI3K in abnormal vascular functions in angiotensin II-infused hypertensive rats

Background: Ang II plays a major role in cardiovascular regulation. Recently, it has become apparent that vascular superoxide anion may play an important role in hypertension development. Treatment with antisense NAD(P)H oxidase or SOD decreased BP in Ang II-infused rats. Wang et al recently reported mice which lack one of the subunits of NAD(P)H oxidase developed hypertension at a much lower extent when compared to the wild type animals infused with Ang II, indicating that superoxide anion contributes to elevation in BP in the Ang II-infused hypertensive model. In the Ang II-infused hypertensive model, altered reactivity of blood vessels is often associated with the elevation of systolic blood pressure. We have observed abnormal tension development and impaired endothelium-dependent relaxation in the isolated aorta of Ang II-infused and DOCA-salt hypertensive rats. Recently, several other cellular signal molecules, including ERK1I2 and PI3K, have been determined to play important roles in the regulation of smooth muscle contraction and relaxation. ERKl/2 and PI3K pathways are also reported to contribute to Ang II induced cell growth, hypertrophy, remodeling and contraction. Moreover, these signaling pathways have shown ROS-sensitive properties. Therefore, the aim of the present study is to investigate the roles of ERKl12 and PI3K in vascular oxidative stress, spontaneous tone and impaired endothelium relaxation in Ang II-infused hypertensive model. Hypothesis: We hypothesize that the activation of ERKl12 and PI3K are elevated in response to an Ang II infusion for 6 days. The elevated activation of phospho-ERKl/2 and PI3K mediated the increased level of vascular superoxide anion, the abnormal vascular contraction and impaired endothelium-dependent vascular relaxation in Ang II-infused hypertensive rats. Methods: Vascular superoxide anion level is measured by lucigenin chemiluminescence. Spontaneous tone and ACh-induced endothelium-dependent relaxation was measured by isometric tension recording in organ chamber. The activity of ERK pathway will be measured by its Western blot of phosphorylation of ERK. PI3K activity was evaluated indirectly by Western blot of the phosphorylation of PDKl, a downstream protein of PI3K signaling pathway. The role of each pathway was also addressed via comparing the responses to the specific inhibitors. Results: Superoxide anion was markedly increased in the isolated thoracic aorta from Ang II-infused rats. There was spontaneous tone developed in rings from Ang II-induced hypertensive but not sham-operated normotensive rats. ACh-induced endothelium-dependent relaxation function is impaired in Ang II-infused hypertensive rats. Superoxide dismutase and NAD(P)H oxidase inhibitor, apocynin, inhibited the abnormal spontaneous tone and ameliorated impaired endothelium-dependent relaxation. The expression of phopho-ERKII2 was enhanced in Ang II-infused rats, indicating the activity of ERK1I2 could be increased. MEK1I2 inhibitors, PD98059 and U126, but not their inactive analogues, SB203580 and U124, significantly reduced the vascular superoxide anion in aortas from Ang II-infused rats. The MEK1I2 inhibitors reduced the spontaneous tone and improved the impaired endothelium-dependent relaxation in aorta of hypertension. These findings supported the role of ERKII2 signaling pathway in vascular oxidative stress, spontaneous tone and impaired endothelium-dependent relaxation in Ang II-infused hypertensive rats. The amount of phospho-PDK, a downstream protein of PI3K was increased in Ang II rats indicating the activity of PI3K activity was elevated. Strikingly, PI3K significantly inhibited the increase of superoxide anion level, abnormal spontaneous tone and restored endothelium-dependent relaxation in Ang II-infused hypertensive rats. These findings indicated the important role of PI3K in Ang II-infused hypertensive rats. Conclusion: ERKII2 and PI3K signaling pathways are sustained activated in Ang II-infused hypertensive rats. The activated ERKII2 and PI3K mediate the increase of vascular superoxide anion level, vascular abnormal spontaneous tone and impaired endothelium-dependent relaxation.

A method of evaluating psychomotor tooth preparation skills in preclinical dental programs

Preclinical and clinical tooth important and significant aspect of preparation is an a dental student's education. The associated procedures rely heavily on the development of particular psychomotor skills. The most common format of instruction and evaluation in tooth preparation at many Dental Faculties, emphasizes the product (tooth preparation) and associates performance with characteristics of this product. This integrated study examines which skills should be developed and how a course of instruction can best be structured to develop the necessary skills. The skills which are identified are those necessary for tooth preparation are selected from a psychomotor taxonomy. The purpose of evaluating these skills is identified. Behavioral objectives are set for student performance and the advisability of establishing standards of performance is examined. After reviewing studies related to learning strategy for dental psychomotor the most suitable tasks as well as articles on instructor effectiveness a model is proposed. A pilot project at the University of Toronto, based on this proposed model is described. The paper concludes wi th a discussion of the implications of this proposed model.

Interrogation of Prisoner - Heaquarters 1st Division, American Expeditionary Forces, 27 May 1918

A prisoner interrogation report dated 27 May 1918. The report reads: "I. PRISONER X. 1st. Battalion, 272 Res. Rogt., 82d Res. 1. CIRCUMSTANCES OF CAPTURE; Captured, while attempting to raid our trenches, at point 1719 at about 7A.M. 2. INFORMATION OBTAINED FROM PRISONER (a) Between point 1814 and point 175242 the German trenches appear to be held by three companies, each numbering 3 platoons, each platoon numbering about 40 men. Each company has 4 light machine guns in the first lines, these machine guns distributed along the first trench (one of them in particular is located at bond in hostile trench at point 17215 and another at about 17245. Each company, furthermore, has one platoon (weak in numbers) in support in the ravine north of Cantigny. These platoons are in dugouts dug into the side of the hill approximately between points 28215 and 2223. Each of these support platoons has two light machine guns at its disposal. Company commanders dugout is at some point along the line of dugouts occupied by the support platoons. Another company commander's dugout (Co.3) is at point 1815 about 15 meters behind the German trench which runs along the edge of the town of Cantigny. There is a communication trench between the cemetery at 2018 and the front line at 18179. It is believed that there is a machine gun at point 17245 kept in a dugout dug under the road. The reserve battalion is believed to be at a fairly great distance from the front (near Bouillancourt). The prisoner, on the other hand, states that it may have been moved up."

Factores socio-culturales y la decisión para el uso de fitoterapia por el paciente diabético

Tesis (Maestría en Enfermería con Especialidad en Salud Comunitaria) UANL

Estructura, sistema de interacción y sujetos sociales : aplicación de un esquema teórico-metodológico a un estudio de caso

Tesis (Maestría en Metodología de las Ciencias) UANL

Vida de Rancé : reformador de la tapa

UANL

Ensayo sobre las revoluciones antiguas

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Mexique et Guatemala

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Estudios sobre la historia de la humanidad

UANL

Principes de Droit Civil Francais

UANL

Principios de derecho civil [por] F. Laurent

UANL

Las aventuras de telémaco, hijo de Ulises

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Atala

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Los cuatro estuardos

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Opiniones y discursos

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