Regular Article
Effect of Ovariectomy and Estrogen Replacement on Cardiovascular Disease in Heart Failure-Prone SHHF/Mcc- fa cp Rats

https://doi.org/10.1006/jmcc.1999.0985Get rights and content

Abstract

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- facp). Development of hypertension was prevented in 3-month-old ovariectomized rats receiving subcutaneous 17 β -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 V1myosin 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 17 β -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.

References (37)

  • EY Adashi

    Transdermal estrogen replacement. In: Adashi EY, Rock JA, Rosenwaks Z (eds). Reproductive Endocrinology, Surgery and Technology. Philadelphia: Lippincott Raven Publishers. 1784–1795

    (1996)
  • H Arai et al.

    Augmented expression of atrial natriuretic peptide in ventricles of spontaneously hypertensive rats (SHR) and SHR-stroke prone

    Circ Res

    (1988)
  • J Bachmann et al.

    Modulation of blood pressure and the renin-angiotensin system in transgenic and spontaneously hypertensive rats after ovariectomy

    J Hypertens

    (1993)
  • V Bittner

    Hypertension in Women

    Curr Op. Neph Hypertens

    (1995)
  • KB Brosnihan et al.

    Effects of chronic hormone replacement on the renin-angiotensin system in cynomolgus monkeys

    J Hypertension

    (1997)
  • C Burnham et al.

    Molecular cloning of rat renin cDNA and its gene

    Proc Natl Acad Sci USA

    (1987)
  • Y Chen et al.

    Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rat

    Hypertension

    (1992)
  • J Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
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    Please address correspondence to: M. Judith Radin, Department of Veterinary Biosciences, 1925 Coffey Road, Columbus, OH 43210, USA. E-mail: [email protected]

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