The mechanisms that stimulate fetal heart growth during anemia are unknown. To examine the hypothesis that adrenal hormones contribute to this process, we determined the effects of adrenalectomy (Adx) on heart growth and the activation of cardiac mitogen-activated protein kinases (MAPKs) in the presence and absence of fetal anemia. To identify mechanisms contributing to the initiation of cardiac growth, the duration of anemia was limited to a period shorter than that previously described to result in increased cardiac mass. Four groups of fetal sheep were studied (Adx-Anemic, Adx-Control, Intact-Anemic, Intact-Control). Anemia was created by daily controlled hemorrhage for 5 days; hearts were collected for analysis at 133 d gestation (term 145 d). Cardiomyocyte morphometry, immunohistochemistry for Ki-67 (proliferation marker), and Western blotting for protein levels of MAPKs and proliferating cell nuclear antigen (PCNA) were performed. Blood pressure, heart rate, heart weight-to-body weight ratio, and cardiomyocyte length and width remained similar among groups throughout the study. PCNA levels in the Adx-Anemic group were twice as high as in any other group (both ventricles, p <0.05). Levels of phosphorylated extracellular signal-regulated kinase (ERK) were ~60% higher in the Intact-Anemic and Adx-Anemic groups, compared with the Intact-Control and Adx-Control groups (p <0.02). These results suggest that adrenal hormones may attenuate fetal cardiomyocyte proliferation in response to anemia (as evidenced by the increased PCNA in Adx-Anemic fetuses) and that phosphorylation of myocardial ERK results from fetal anemia, irrespective of the status of the fetal adrenal gland.
ASJC Scopus subject areas
- Physiology (medical)