Effect of ovariectomy and estrogen replacement on cardiovascular disease in heart failure-prone SHHF/Mcc-fa(cp) rats

Leslie C. Sharkey, Bethany J. Holycross, Sonhee Park, Laura J. Shiry, Toni M. Hoepf, Sylvia A. McCune, Judith M. Radin

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56 Scopus citations


The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic peptide (ANP) and components of the renin angiotensin system in spontaneously hypertensive heart failure rats (SHHF/Mcc-fa(cp)). Development of hypertension was prevented in 3-month-old ovariectomized rats receiving subcutaneous 17β-estradiol implants (EST) compared to ovariectomized (OVX) and controls (CON). EST had the least left ventricular hypertrophy, CON were intermediate, and OVX had the most (P < 0.05), correlating well with systolic blood pressure. OVX had significantly lower percentage V1 myosin isoform compared to EST and CON, indicating reversion to a more immature phenotype associated with hypertrophy. Similarly, OVX had decreased percentage left ventricular shortening fraction by echocardiography compared to EST and CON. These changes were not accompanied by alterations in plasma ANP, or in expression of mRNA for left ventricular ANP, renal renin, or hepatic angiotensinogen. Serum angiotensin converting enzyme activity was lower in EST compared to CON or OVX. When 17β-estradiol was given to 17-month-old rats that had naturally ceased estrous cycling, there was no effect on hypertension, progression of cardiac functional decline, or survival. In conclusion, estradiol treatment given prior to the development of hypertension in SHHF prevented left ventricular hypertrophy and hypertension. Development of congestive heart failure was not delayed if 17β-estradiol was begun in the post-menopausal period. Effectiveness of estrogen therapy may depend on age or whether hypertension is already established at the time treatment is begun.

Original languageEnglish (US)
Pages (from-to)1527-1537
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Issue number8
StatePublished - Aug 1999

Bibliographical note

Funding Information:
This work was supported in part by US Public Health Service Grant HL48835. Salaries and research support was also provided in part by state and federal funds appropriated to the Ohio Agricultural Research and Development Center, Ohio State University.


  • Angiotensin converting enzyme
  • Atrial natriuretic peptide
  • Estradiol
  • Hypertension
  • Left ventricular fractional shortening
  • Left ventricular hypertrophy
  • Myosin isozyme
  • Renin angiotensin system


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