Low dose but not high dose of 17â‐estradiol prevents cardiac fibrosis in DOCA‐salt model of hypertension in rats

Abstract

The current study was designed to investigate the effects of 17ß‐estradiol (E2) on cardiac remodeling. To address this issue, we evaluated cardiac fibrosis and hypertrophy in deoxycorticosterone acetate (DOCA)‐salt treated rats with chronic, six‐week administration of two different doses of E2. Female SD rats were ovariectomized bilaterally (Ovex). Hypertension was induced by subcutaneous implantation of DOCA‐pellet in uninephrectomized animals, which were later maintained on 1% saline. The rats were randomly assigned to one of the following groups: Ovex control; Ovex + DOCA; Ovex + DOCA + E2 (low dose); or Ovex + DOCA + E2 (high dose). Blood pressure measurement showed a significant increase in DOCA treated rats over a six week period, which was not altered by estrogen replacement. No difference in cardiac function was observed among the different groups when assessed using isolated rat heart Langendorff apparatus. Both doses of estrogen attenuated cardiac hypertrophy observed in the DOCA treated animals. However, when measuring cardiac fibrosis induced by DOCA treatment, only the low dose E2 therapy showed a protective effect. The high dose E2 therapy failed to exhibit anti‐fibrotic effects. These findings suggest that estrogen replacement therapy may have blood‐pressure independent cardio‐protective effects that are dose‐dependent.