Consequences d'un environnement foetal defavorable sur le systeme cardiovasculaire de rat adulte (French and English text)

Epidemiological studies have shown a link between low birth weight and adult diseases. Previous studies in our laboratory have reported that low-sodium diet given to the dams for the last week of gestation (out of 3) results in decreased uterine vessels diameter, reduced placental weight and foetal weight and height. These data suggests decreased placental perfusion and adverse intrauterine environment. In the present thesis, we hypothesized that adverse intrauterine environment leads to the programming of adult diseases.; Our first objective was to characterize the animal model. We have observed that dams receiving the low-sodium diet were giving birth to newborns of lower weight (experimentals). At 12 weeks of age, these animals were still smaller then controls. Using the indirect tail-cuff measuring system, we have shown that systolic blood pressure was increased in experimental animals when compared to controls. In experimental males, plasma renin activity (PRA) and plasma urea concentrations were increased. In experimental females, we observed increased PRA, decreased plasma aldosterone concentrations and elevated urea and creatinine plasma levels. Moreover, experimental females showed increased left cardiac ventricle to body weight ratio when compared to female controls. This result suggest cardiac hypertrophy. These data suggest that elevation of systolic blood pressure observed in experimental animals was associated with renal and cardiac dysfunction and alterations of the renin-angiotensin-aldosterone system.; In the second part of the study, the specific aims were to explore the cellular and molecular alterations of cardiac hypertrophy observed in experimental females. By using confocal microscopy, we showed increased cardiomyocytes volume secondary to increase myocyte depth. These myocytes had also longer sarcomeres. Increase in mRNA expression of the atrial natriuretic peptide and the atrial isoform of the myosin light chain genes was observed in the left cardiac ventricle of experimental females after DNA microarray experiments. Moreover, beta1 subunit of the Na+/K+/ATPase was decreased at the mRNA and protein levels and this was accompanied by reduced cardiomyocyte contractility and aconitase activity. Reduction in this tricarboxylic cycle enzyme activity reflects increased oxidative stress. We thus propose that oxidative stress may be part of the reason for cellular and molecular alterations seen in cardiac hypertrophy found in experimental adult females. (Abstract shortened by UMI.)...