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Objective Elevated aldosterone is associated with increased risk of atherosclerosis complications, whereas treatment with mineralocorticoid receptor (MR) antagonists decreases the rate of cardiovascular events. Here we test the hypothesis that aldosterone promotes early atherosclerosis by modulating intercellular adhesion molecule-1 (ICAM-1) expression and investigate the molecular mechanisms by which aldosterone regulates ICAM-1 expression. Methods and results Apolipoprotein-E (ApoE)−/− mice fed an atherogenic diet and treated with aldosterone for 4 weeks showed increased vascular expression of ICAM-1, paralleled by enhanced atherosclerotic plaque size in the aortic root. Moreover, aldosterone treatment resulted in increased plaque lipid and inflammatory cell content, consistent with an unstable plaque phenotype. ApoE/ICAM-1 double knockout (ApoE−/−/ICAM-1−/−) littermates were protected from the aldosterone-induced increase in plaque size, lipid content and macrophage infiltration. Since aldosterone is known to regulate ICAM-1 transcription via MR in human endothelial cells, we explored MR regulation of the ICAM-1 promoter. Luciferase reporter assays performed in HUVECs using deletion constructs of the human ICAM-1 gene promoter showed that a region containing a predicted MR-responsive element (MRE) is required for MR-dependent transcriptional regulation of ICAM-1. Conclusions Pro-atherogenic effects of aldosterone are mediated by increased ICAM-1 expression, through transcriptional regulation by endothelial MR. These data enhance our understanding of the molecular mechanism by which MR activation promotes atherosclerosis complications.

The detonability limits and detonation behavior were studied for a finely ground ammonium perchlorate (AP). The typical finite diameter D vs rho sub o curve is non-linear and exhibits a maximum in detonation velocity. The failure curve d sub c (diameter) vs rho sub c (critical density) shows a monotonic increase in d sub c with rho sub c in the range rho sub o 1.0 g/cc and is opposite in trend to that for TNT.

The detonation velocity and critical density of ammonium perchlorate (AP) increased, whereas the critical diameter decreased, with decreasing particle size. Relative reaction times varied as the particle diameter. Ideal detonation velocities were unaffected. The regular gap test is recommended for AP and the gradient of its '50% gap pressure vs. loading density' curve at higher porosities is shown to be like that of the TNT curve.

A second calibration of the gap test was made with a pentolite donor replacing the tetryl donor of the standardized test. The calibration consisted of measuring the attenuation of the shock velocity in a Plexiglas rod, and calculating the corresponding shock pressure as a function of gap distance.

Precise continuous wire data obtained from shock-to-detonation transitions in cast DINA show that the voltage-time records cannot be interpreted directly as run length and total delay time. Corrections made for a thick conducting zone of reacted explosive needed to close the wire circuit give reasonable results. (Author), See also AD-419 053.

A transformation equation was derived whereby the data from smear camera records of the peripheral detonation of a short (L/D of 2.5) tetryl charge can be interpreted to obtain a detonation velocity measurement. The results are in excellent agreement with the values measured along the axis as well as with those published in the literature. (Author)