It has recently been shown that glomerular mesangial injury is associated with increases in renal cortical reactive oxygen species (ROS) levels in rats treated chronically with aldosterone and salt. This study was conducted to determine the mechanisms responsible for aldosterone-induced ROS production in cultured rat mesangial cells (RMC). Oxidative fluorescent dihydroethidium was used to evaluate intracellular production of superoxide anion (O 2 ؊ ) in intact cells. The lucigeninderived chemiluminescence assay was used to determine NADPH oxidase activity. The staining of dihydroethidium was increased in a dose-dependent manner by aldosterone (1 to 100 nmol/L) with a peak at 3 h in RMC. Aldosterone A growing body of evidence supports a role for aldosterone in the progression of renal injury (1-4). In rats, chronic administrations of aldosterone and salt led to severe proteinuria and glomerular injury (5,6). Similarly, exogenous infusion of aldosterone reversed the renoprotective effects of angiotensin-converting enzyme (ACE) inhibitors in remnant kidney hypertensive rats (7) and stroke-prone, spontaneously hypertensive rats (SHRSP) (8). In addition, treatment with the mineralocorticoid receptor (MR) antagonists ameliorated glomerular injury in SHRSP (9) and in rats treated with angiotensin II (AngII) and nitric oxide synthase inhibitor (10), cyclosporine A (11) or radiation (12), independent of BP reduction. In patients with chronic renal failure (13) and early diabetic nephropathy (14), addition of a nonselective MR antagonist, spironolactone, to ACE inhibitors did not exert hemodynamic effects, but markedly reduced urinary excretion rate of protein (U protein V). These observations suggest that aldosterone has direct deleterious effects on the kidney via activation of the MR. However, the mechanisms responsible for the aldosterone/MR-induced renal injury remain undetermined.Recent studies have indicated the potential participation of reactive oxygen species (ROS) in the pathophysiology of aldosterone-induced cardiovascular tissue injury (5,(15)(16)(17)(18)(19)(20)(21)(22). In aldosterone/salt-treated hypertensive rats, vascular NADPH oxidase activity and ROS production were markedly increased (15,16). In these animals, treatment with an NADPH oxidase inhibitor, apocynin, prevented BP elevation and cardiovascular hypertrophy (17). It was also shown that treatment with a selective MR antagonist, eplerenone, improved endothelial dysfunction and reduced vascular superoxide anion (O 2 Ϫ ) generation in diet-induced atherosclerosis (18). Similarly, eplerenone reduced aortic atherosclerotic lesions and O 2 Ϫ generation in peritoneal macrophages of apolipoprotein E-deficient mice (19,20). Mazak et al. (21) showed that aldosterone potentiates AngII-induced signaling in vascular smooth muscle cells, and that these effects of aldosterone were blocked by antioxidants. The authors also showed that spironolactone decreased NADPH

Abstract-Treatment with cyclosporine A (CysA), a potent immunosuppressive agent, is associated with systemic and renal vasoconstriction, leading to hypertension. The present study was conducted to elucidate the contribution of angiotensin II (Ang II) to CysA-induced hypertension and reactive oxygen species (ROS) generation. CysA (30 mg/kg per day SC), given for 3 weeks in rats, increased systolic blood pressure (SBP) from 119Ϯ2 to 145Ϯ3 mm Hg (nϭ7). Plasma and kidney Ang II levels were significantly higher in CysA-treated rats (136Ϯ10 fmol/mL and 516Ϯ70 fmol/g) than in vehicle-treated (1 mL olive oil) rats (76Ϯ10 fmol/mL and 222Ϯ21 fmol/g, nϭ7). CysA treatment increased AT 1 receptor protein expression in the aorta (by 251Ϯ35%), whereas it was reduced in the kidney (by Ϫ32Ϯ4%). Superoxide anion production in aortic segments and kidney thiobarbituric acid-reactive substance (TBARS) contents were higher in CysA-treated rats (26Ϯ2 counts/min per milligram and 37Ϯ3 nmol/g) than in vehicle-treated rats (17Ϯ1 counts/min per milligram and 24Ϯ3 nmol/g). Concurrent administration of an AT 1 receptor antagonist, valsartan (30 mg/kg per day, in drinking water), to CysA-treated rats (nϭ7) significantly decreased SBP (113Ϯ4 mm Hg) and prevented increases in vascular superoxide (16Ϯ2 counts/min per milligram) and kidney TBARS contents (21Ϯ3 nmol/g). Similarly, treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6,-tetramethylpiperidine-N-oxyl (Tempol; 3 mmol/L in drinking water, nϭ7), prevented CysA-induced increases in SBP (115Ϯ3 mm Hg), vascular superoxide (16Ϯ1 counts/min per milligram), and kidney TBARS contents (19Ϯ2 nmol/g). These data suggest that ROS generation induced by augmented Ang II levels contributes to the development of CysA-induced hypertension. Key Words: angiotensin antagonist Ⅲ antioxidants Ⅲ receptors, angiotensin II Ⅲ renin C yclosporine A (CysA) is a potent immunosuppressive agent and is widely used after organ transplantation and in the treatment of several autoimmune diseases. 1 However, its clinical use is frequently complicated by systemic and renal vasoconstriction, leading to arterial hypertension. 2 Although numerous factors have been implicated, 2 several lines of evidence suggest an involvement of the renin-angiotensin system in the development of CysA-induced hypertension. 3-10 Increased plasma renin activity and renin content in kidney tissues were observed in rats treated with long-term CysA 4 . It was also shown that CysA treatment augmented angiotensin II (Ang II)-induced vasoconstriction in isolated arterioles 5 or calcium response in vascular smooth muscle cells. 6 Lasssila et al 7,8 demonstrated that treatment with an ACE inhibitor or an AT 1 receptor antagonist abrogates CysA-induced hypertension and vascular dysfunction in spontaneously hypertensive rats (SHR) fed a high salt diet. Further clinical studies showed that treatment with an ACE inhibitor or an AT 1 receptor antagonist reduced blood pressure in hypertensive CysA-treated patients after renal transplantation. 9,10...

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Dangerous rocks are among the most significant factors in analyzing the stability of high slopes, and are the main geological hazards on such slopes. These rocks are typical spatial blocks. The unstable failure of dangerous rocks poses evident spatial features. Consequently, their stability should be calculated by considering it as a three-dimensional (3-D) problem. In this research, the general block method of fractured rock mass and 3-D discontinuous deformation analysis (DDA) are used to study the stability of dangerous rocks on the slope of a hydropower station. The general block method of fractured rock mass is used to generate dangerous rocks and to assess the geometric mobility of blocks. The progressive unstable failure of dangerous rocks is also analyzed. Moreover, 3-D DDA is implemented to examine the stability of dangerous rocks, including the regularity of their unstable failure. The failure sequence of each batch of blocks estimated by general block theory is the same as that in the results of 3-D DDA. The decrease in the shear parameters of the structural plane shortens the time interval of failures, but increases the number and capacity of blocks.

For the task of evaluating the inclusions in the steel specimen under high efficiency testing condition, it is important to make it clear that what testing sensitivity the ultrasonic method can reach for a specimen of large size, especially a thick one. In this paper, this problem is researched and discussed. Before experimental researching, we simulated the focused ultrasonic field formed in the steel specimen by DPSM (Distributed Point Source Method), the frequency ranges from 7.5MHz to 15MHz. DPSM analysis reveals that the ultrasonic field of certain strength can be formed in the thick steel specimen of coarse grain, and the focused transducer of 15MHz is suitable for the inclusion evaluation of thick steel specimens. Then, with the help of a precise micro-step C-scan equipment and the 15Mhz transducer (13mm Diameter, 255mm focal length), the ultrasonic test sensitivity research work was carried out on the thick steel specimen, by the way of testing the inclusions which's size were as tiny as possible, and located as far from the testing surface as possible, and at last, the ultrasonic detection results were testified by mechanical dissection. The dissected inclusions which can be tested are grouped into 8 different grades by its size, it is demonstrated that the deepest inclusion can be tested in the specimen is about 80mm beneath the testing surface by ultrasonic method, and reflection area is about 0.02mm2, equivalent to a circle inclusion of diameter 0.16mm. In addition, there are some semi-quantitative relationships can be drawn among the grade of inclusion, the location depth of inclusion in the specimen, and the reflected ultrasonic signal strength from the inclusion, this give a way of evaluating the inclusion size in the thick steel specimen by the focused ultrasonic method.