Faculty Collaboration Database

17beta-Estradiol modulates local cardiac renin-angiotensin system to prevent cardiac remodeling in the DOCA-salt model of hypertension in rats. Peptides 2009 Dec;30(12):2309-15

Date

09/15/2009

Pubmed ID

19747516

DOI

10.1016/j.peptides.2009.09.005

Scopus ID

2-s2.0-70449632336 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

Ventricular remodeling can play a detrimental role in the progression of cardiovascular diseases, leading to heart failure. The current study was designed to investigate the effects of 17beta-estradiol (E2) on cardiac remodeling. Cardiac fibrosis and hypertrophy were examined in deoxycorticosterone acetate (DOCA)-salt treated rats with chronic, six-week administration of two different doses of E2. Bilaterally ovariectomized (Ovex) female Sprague-Dawley rats were randomly assigned to one of the following groups: Ovex-control; Ovex-DOCA; Ovex-DOCA+low-dose E2 (1.66 microg/day); or Ovex-DOCA+high-dose E2 (2.38 microg/day). All DOCA-treated rats were uninephrectomized and drinking water was replaced by 0.15M NaCl solution for the remainder of the study period. DOCA-salt treatment resulted in a significant increase in blood pressure, which was not altered by estrogen replacement. Histological examinations revealed marked cardiac remodeling (both ventricular hypertrophy and interstitial fibrosis) with DOCA treatment, which was attenuated in animals receiving estrogen therapy. Western blot analysis demonstrated increased cardiac levels of angiotensin converting enzyme (ACE) with DOCA treatment, which was attenuated by E2 replacement. Furthermore, increased levels of cardiac angiotensin converting enzyme 2 (ACE2) protein were observed in animals receiving high-dose E2 replacement. These findings suggest that physiologically relevant estrogen replacement therapy has blood pressure-independent cardioprotective effects, which are possibly mediated through modulation of the cardiac renin-angiotensin system.

Author List

Shenoy V, Grobe JL, Qi Y, Ferreira AJ, Fraga-Silva RA, Collamat G, Bruce E, Katovich MJ

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Blotting, Western
Body Weight
Cardiomegaly
Estradiol
Estrogen Replacement Therapy
Female
Hypertension
Myocardium
Organ Size
Ovariectomy
Peptidyl-Dipeptidase A
Random Allocation
Rats
Rats, Sprague-Dawley
Renin-Angiotensin System