Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor.

Non-physiological activation of the mineralocorticoid receptor (MR), e.g. by aldosterone under conditions of high salt intake, contributes to the pathogenesis of cardiovascular diseases, although beneficial effects of aldosterone also have been described. The epidermal growth factor receptor (EGFR) contributes to cardiovascular alterations and mediates part of the MR effects. Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals. We hypothesize that moderate high aldosterone/NaCl, at normal blood pressure, affects the cardiovascular system depending on cardiovascular EGFR. Therefore we performed an experimental series in male and female animals each, using a recently established mouse model with EGFR knockout in vascular smooth muscle cells and cardiomyocytes and determined the effects of a mild-high aldosterone-to-NaCl constellation on a.o. marker gene expression, heart size, systolic blood pressure, impulse conduction and heart rate. Our data show that (i) cardiac tissue of male but not of female mice is sensitive to mild aldosterone/NaCl treatment, (ii) EGFR knockout induces stronger cardiac disturbances in male as compared to female animals and (iii) mild aldosterone/NaCl treatment requires the EGFR in order to disturb cardiac tissue homeostasis whereas beneficial effects of aldosterone seem to be independent of EGFR.

Do in situ forming PLG/NMP implants behave similar in vitro and in vivo? A non-invasive and quantitative EPR investigation on the mechanisms of the implant formation process.

Electron paramagnetic resonance (EPR) spectroscopy was applied to monitor non-invasively the formation of in situ forming implants in vitro and in vivo after the administration of poly(lactide-co-glycolide) (PLGA)/N-methyl-pyrrolidone (NMP) solutions. The nitroxide spin probe 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TB) was incorporated in polymer solutions and samples were incubated in 0.1 M phosphate buffer (pH 7.4) at 37 degrees C or injected subcutaneously in the femoral of BALB/c mice. EPR permitted the direct and continuous determination of the NMP-water exchange during implant formation both in vitro and in living mice. The formation of the implant structure followed a two phase mechanism: over 75% of the polymer precipitated immediately after injection within the first 30 min and formed a solid shell. The subsequent moderate solidification of the implants was governed by diffusion and was completed after 24 h. The replacement of the organic solvent NMP by water was determined by polarity shifts within the implant and could be quantified. Both the kinetic of NMP-water exchange and polymer precipitation showed good in vitro-in vivo correlation.