201 Stagedependent activation of cell cycle and apoptosis mechanisms in the right ventricle by pressure overload

induction and development of cardiac hypertrophy (CH). In this study we investigated, whether calcineurin might be involved in the development of the left/right ventricle differences in NE-induced CH. Female Sprague-Dawley rats were treated with continuous NaCl-infusion (controls, C) or NE-infusion (0.1 mg/kg.h i.v.) for 12 and 96 hours. The effect of NE-treatment was documented by changes in the LV and RV function and in the change in the LV weight to body weight (LVW/BW) and RV weight to body weight (RVW/BW) ratios. Western blots were done with calcineurin-A (Cn-A) antibody (Stressgene Biotechnologies). We used the rat brain tissue extract as positive control for calcineurin antibody. After 12h of NE-treatment the RV systolic pressure (C 28.7±4.1, NE 65.9±2.7 mm Hg), heart rate (C 381±10.5, NE 490±12.7 beats/min), RV dP/dt max (C 1927±462.2, NE 5380±508 mm Hg/s) as well as LV dP/dt max (C 9276±1192, NE 18405±1538 mm Hg/s) were significantly increased (all p < 0.01). The LVW/BW ratio, but not the RVW/BW ratio was significantly increased in NE-treated rats (p < 0.05). Also the mRNA for atrial natriuretic factor (ANP), a marker of hypertrophy, was significantly increased in the LV only as shown previously by Barth et al. (J Mol Cell Cardiol 32, 2000, 273-284). At this time point neither in the LV, nor in the RV was the Cn-A protein significantly changed after NEtreatment. After 96h of NE-treatment heart function remained elevated to a similar extent as after 12h. The LVW/BW, but not the RVW/BW ratio was significantly increased (from 2.19±0.07 to 2.5±0.05, p < 0.01). There was a significant increase in the Cn-A protein in the LV only (factor of change for LV 1.49±0.26, p < 0.05). This increase was also significantly different from the change in the RV (factor of change 1.01 ± 0.15; p < 0.05). Thus, calcineurin seems to be differently expressed in the left and right ventricle in the NE-induced hypertrophy and may play a role in the signalling for ventricle-specific cardiac hypertrophy.