Regulation of components of the brain and cardiac renin-angiotensin systems by 17 -estradiol after myocardial infarction in female rats

Dean, Stephanie A., Junhui Tan, Roselyn White, Edward R. O’Brien, and Frans H. H. Leenen. Regulation of components of the brain and cardiac renin-angiotensin systems by 17 -estradiol after myocardial infarction in female rats. Am J Physiol Regul Integr Comp Physiol 291: R155–R162, 2006. First published February 2, 2006; doi:10.1152/ajpregu.00497.2005.—The present study tested the hypothesis that 17 -estradiol (E2) inhibits increases in angiotensinconverting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Agematched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy subcutaneous vehicle treatment (OVX Veh), or 3) OVX subcutaneous administration of a high dose of E2 (OVX high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2–3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20–40%) in OVX high-E2 MI rats, somewhat less (10–15%) in ovary-intact MI rats, and least ( 10–15%) in OVX Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX Veh rats and decreased in the OVX high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher ( 20%) in OVX Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.