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

The importance of endogenous and exogenous estrogen levels to the developme nt of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertens ion, cardiac hypertrophy ventricular function, and gene expression for atri al natriuretic peptide (ANP) and components of the renin angiotensin system in spontaneously hypertensive heart failure rats (SHHF/Mcc-fa(cp)). Develo pment of hypertension was prevented in 3-month-old ovariectomized rats rece iving subcutaneous 17 beta-estradiol implants (EST) compared to ovariectomi zed (OVX) and controls (CON), EST had the least left ventricular hypertroph y, CON were intermediate, and OVX had the most (P < 0.05), correlating well with systolic blood pressure. OVX had significantly lower percentage V-1 m yosin isoform compared to EST and CON, indicating reversion to a more immat ure phenotype associated with hypertrophy. Similarly, OVX had decreased per centage left ventricular shortening fraction by echocardiography compared t o 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 hep atic angiotensinogen. Serum angiotensin converting enzyme activity was lowe r in EST compared to CON or OVX. When 17 beta-estradiol was given to 17-mon th-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 hyperten sion in SHHF prevented left ventricular hypertrophy and hypertension. Devel opment of congestive heart failure was not delayed if 17 beta-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 t reatment is begun. (C) 1999 Academic Press.