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Estrogen delays the progression of salt-induced cardiac hypertrophy by influencing the renin-angiotensin system in heterozygous proANP gene-disrupted mice

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Abstract

Left ventricular hypertrophy is considered an independent risk factor for cardiac morbidity and mortality, and many studies have shown that women have a lower incidence of left ventricular hypertrophy even after correcting for numerous risk factors. This cardio-protective effect seen in women has been attributed to estrogen, which likely modulates specific growth-promoting systems such as the renin-angiotensin system, and in turn may lead to the prevention of left ventricular hypertrophy. Furthermore, the underlying mechanisms responsible are poorly understood. The aim of the present study was to examine the effect of estrogen in relation to its impact on the development of left ventricular hypertrophy through its interaction with the renin-angiotensin system by using the proANP heterozygous (ANP +/−) mouse as a model of salt-sensitive cardiac hypertrophy. Male, female ANP +/− mice and also ovariectomized female ANP +/− mice treated with oil or estrogen, were fed either a normal or high-salt diet. All four groups exhibited a general suppression of the renin-angiotensin system under the high salt challenge. However, after the 5-week treatment period, marked left ventricular hypertrophy was noted only in the male and oil-injected ovariectomized female ANP +/− mice treated with high salt. Collectively, we provide direct evidence that the differences in cardiac hypertrophy between genders in ANP +/− mice is attributed to estrogen. Furthermore, estrogen may play a key role in slowing down the progression of salt-induced left ventricular hypertrophy in ANP +/− mice, in part, independent of the classical systemic renin-angiotensin system and possibly through other pathways.

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Acknowledgments

The authors would like to thank Dr. K.E. Wynne-Edwards and Mr. Y. Kiparissis from the Department of Biology at Queen’s University for performing the estrogen immunoassay for us. We would also like to thank Dr. E. Angelis for providing valuable comments and reviewing this manuscript. Financial support of this research was provided by a grant-in-aid from the Heart and Stroke Foundation of Ontario (HSFO #T6140), and the Garfield Kelly Cardiovascular Research and Development Fund from the Faculty of Health Sciences at Queen’s University.

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  1. Department of Anatomy and Cell Biology, Queen’s University, Room 850, Stuart St., Botterell Hall, Kingston, ON, Canada, K7L 3N6

    S. Jeson Sangaralingham, M. Yat Tse & Stephen C. Pang

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  1. S. Jeson Sangaralingham
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  2. M. Yat Tse
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  3. Stephen C. Pang
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Correspondence to Stephen C. Pang.

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Sangaralingham, S.J., Tse, M.Y. & Pang, S.C. Estrogen delays the progression of salt-induced cardiac hypertrophy by influencing the renin-angiotensin system in heterozygous proANP gene-disrupted mice. Mol Cell Biochem 306, 221–230 (2007). https://doi.org/10.1007/s11010-007-9573-8

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  • DOI: https://doi.org/10.1007/s11010-007-9573-8

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