Abstract
Normotensive female rats exhibit age-related decreases in estrous cyclicity and increases in blood pressure. In spontaneously hypertensive rats, estrogens, including dietary phytoestrogens, prevent or attenuate the increased blood pressure associated with estrogen depletion. The present studies examine the effects of ovariectomy (OVX) at either 3 or 10 mo of age. Although blood pressure increases from 3 to 9 mo, OVX at 3 mo of age has no added effect—despite the fact that OVX (compared to ovary-intact) rats weighed significantly more. In contrast, aging from 10 to 16 mo is associated with a further increase in blood pressure, which is potentiated by estrogen depletion. Removal of dietary phytoestrogens exacerbated the hypertensive effects of OVX in these middle-aged rats. As in younger rats, estrogen depletion at 10 mo of age was associated with greater weight gain. Whereas estrogen depletion at 3 mo of age was without effect on fluid intake over the next 6 mo, OVX at 10 mo of age was associated with decreased fluid intake. In a final study, rats were OVX at 3 mo of age with estradiol (E2) treatment initiated at 10 mo of age. Long-term OVX (>10 mo) was associated with increased blood pressure and mortality at 14–16 mo of age. Circulating levels of E2 were decreased by OVX. Plasma aldosterone was increased by OVX, an effect which was prevented by either E2 or phytoestrogens. Neither E2 nor aldosterone was affected by age. These data indicate that (a) the physiological effects of estrogen depletion vary with age; (b) phytoestrogens in the diet exert some protective effects; and (c) long-term OVX in the absence of hormone replacement is associated with premature mortality. We suggest that chronic increases in aldosterone and sympathetic tone underlie the hypertensive effects of estrogen depletion.
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References
Pickering, S. G. (1995). In: Hypertension: pathophysiology, diagnosis, and management, 2nd ed. Laragh, J. H. and Brenner, B. M. (eds.). Raven: New York.
Kotchen, J. M., McKean, H. E., and Kotchen, T. A. (1982). Hypertension 4, 128–134.
Burt, V. L., Whelton, P., and Roccella, E. J. (1995). Hypertension 25, 305–314.
Fentie, I. H., Greenwood, M. M., Wyss, J. M., and Clark, J. T. (2004). Endocrine 25, 15–22.
Rossouw, J. E., Anderson, G. I., Prentice, R. L., and Writing Group for the Women’s Health Initiative Investigators. (2002). JAMA 288, 321–333.
Stefanick, M. L., Cochrane, B. B., Hsia, J., Barad, D. H., Liu, J. H., and Johnson, S. R. (2003). Ann. Epidemiol. 13(9 Suppl), S78-S86.
Anderson, G. I., Limacher, M., Assaf, A. R., Bassford, T., and Women’s Health Initiative Steering Committee. (2004). JAMA 291, 1701–1712.
Fletcher, S. W. and Colditz, G. A. (2002). JAMA 288, 2824–2825.
Simpkins, J. W., Rajakumar, G., Zhang, Y. Q., et al. (1997). J. Neurosurg. 87, 724–730.
Wise, P. M., Dubal, D. B., Wilson, M. E., Rau, S. W., and Bottner, M. (2001). Endocrinology 142, 969–973.
McEwen, B. S. (2001). J. Appl. Physiol. 91, 2785–2801.
McCollough, L. D. and Hurn, P. D. (2003). Trends Endocrinol. Metab. 14, 228–235.
Brownley, K. A., Hinderliter, A. L., West, S. G., et al. (2004). Am. J. Obstet. Gynecol. 190, 1052–1058.
Spence, J. D. (1996). J. Hypertension Suppl. 14, 139–145.
Staessen, J., Bulpitt, C. J., Fagard, R., Lijnen, P., and Amery, A. (1989). J. Human Hypertension 3, 427–433.
Kannel, W. B. (1995). Hypertension Res. 18, 171–196.
Scuteri, A., Lakatta, E. G., Bos, A. J., and Fleg, J. L. (2001). Aging 13, 122–130.
Hunt, B. E., Taylor, J. A., Hamner, J. W., Gagnon, M., and Lispsitz, L. A. (2001). Circulation 103, 2909–2914.
Matthews, K. A., Flory, J. D., Owens, J. F., Harris, K. F., and Berga, S. L. (2001). Psychophysiology 38, 391–398.
Weitz, G., Elam, M., Born, J., Fehm, H. L., and Dodt, C. (2001). J. Clin. Endocrinol. Metab. 86, 344–348.
Hersh, A. L., Stefanick, M. L., and Stafford, R. S. (2004). JAMA 291, 47–53.
Sorensen, M. B., Collins, P., Ong, P. J. L., et al. (2002). Circulation 106, 1646–1651.
Higashi, Y., Sanada, M., Sasaki, S., et al. (2001). Hypertension 37, 651–657.
Alecrin, I. N., Aldrighi, J. M., Caldas, M. A., Gebara, O. C., Lopes, N. H., and Ramires, J. A. (2004). Heart 90, 777–781.
Kuiper, G. G., Carlsson, B., Grandien, K., et al. Endocrinol. 138, 863–870.
Kuiper, G. G., Lemmen, J. G., Carlsson, B., et al. (1998). Endocrinol. 139, 4252–4263.
Chang, H. C., Churchwell, M. I., Delclos, K. B., Newbold, R. R., and Doerge, D. R. (2000). J. Nutr. 130, 1963–1970.
Wyss, J. M. and Carlson, S. H. (2003). Curr. Hyperten. Rep. 5, 241–246.
Fang, Z., Carlson, S. H., Chen, Y. F., Oparil, S., and Wyss, J. M. (2001). Am. J. Physiol. 281, R1934-R1939.
Lu, J. K. H., Hopper, B. R., Vargo, T. M., and Yen, S. C. C. (1978). Biol. Reprod. 21, 191–201.
Wise, P. M., Weiglund, N. G., Scarbrough, K., Larson, G. H., and Llyod, J. M. (1989). In: Ovarian secretions and cardiovascular and neurological function. Naftonlin, F., Gutmann, J. N., DeCherney, A. H., and Sarrell, P. M. (eds.). Raven Press: New York.
Fang, Z. and Wyss, J. M. (2000). FASEB J. 14, A662.
Williams, J. K., Young, D. K., Adams, M. R., Chen, M. F., Myers, A. K., and Ramwell, P. W. (1994). J. Pharmacol. Exper. Therap. 271, 671–676.
Clarkson, T. B., Anthony, M. S., Williams, J. K., Honore, E. K., and Cline, J. M. (1999). Proc. Soc. Exper. Biol. Med. 217, 365–368.
Fisher, N. D., Ferri, C., Bellini, C., et al. (1997). Hypertension 29, 980–985.
Peng, N., Clark, J. T., Wei, C. C., and Wyss, J. M. (2003). Hypertension 41, 1164–1167.
Wyss, J. M., Yang, R. H., and Oparil, S. (1990). J. Auton. Nerv. Sys. 31, 21–30.
Squadrito, F., Altavilla, D., Squadrito, G., et al. (2000). Cardiovasc. Res. 45, 454–462.
Li, H.-F., Wang, L.-de, and Qu, S.-yi. (2004). Acta Pharmacol. Sin. 25, 313–318.
Martin, D. S., Breitkopf, N. P., Eyster, K. M., and Williams, J. L. (2001). Am. J. Physiol. 281, R553-R560.
Kreijkamp-Kaspers, S., Kok, L., Bots, M. L., Grobbee, D. E., and van der Schouw, Y. T. (2004). J. Hypertens. 22, 1381–1388.
Teede, H. J., McGrath, B. P., DeSilva, L., Cehun, M., Fassoulakis, A., and Nestel, P. J. (2003). Arteriscler. Thromb. Vasc. Biol. 23, 1066–1071.
de Kleijn, M. J., van der Schouw, Y. T., Wislon, P. W., Grobbee, D. E., and Jacques, P. (2002). J. Nutr. 132, 276–282.
Powers, J. B. and Valenstein, E. S. (1972). Science 175, 1003–1005.
Patisaul, H. B., Dindo, M., Whitten, P. L., and Young, L. J. (2001). Endocrinol. 142, 2946–2952.
Patisaul, H. B., Luskin, J. R., and Wilson, M. E. (2004). Horm. Behav. 45, 270–277.
Patisaul, H. B., Melby, M., Whitten, P. L., and Young, L. J. (2002). Endocrinol. 143, 2189–2197.
Kuroski de Bold, M. L. (1999). Cardiovasc. Res. 41, 524–531.
Roesch, D. M., Tian, Y., Zheng W., Shi, M., Verbalis, J. G., and Sandberg, K. (2000). Endocrinol. 141, 4629–4636.
Seely, E. W., Brosnihan, K. B., Jeunemaitre, X., et al. (2004). Clin. Endocrinol. 60, 315–321.
Zacharieva, S., Kirilov, G., Kalinov, K., et al. (2002). Gynecol. Endocrinol. 16, 461–467.
Tang, F. (1985). Horm. Metbol. Res. 17, 507–509.
Iams, S. G., McMurty, J. P., and Wexler, B. C. (1979). Endocrinol. 104, 1357–1363.
Chobanian, A. V., Bakris, G. L., Black, H. R., et al. (2003). Hypertens. 42, 1206–1252.
Ribeiro, J. C., Guerra, S., Oliveira, J., Anderson, L. B., Duarte, J. A., and Mota, J. (2004). Am. J. Hum. Biol. 16, 556–562.
Ladeia, A. M. and Guimaraes, A. C. (2003). Prevent. Cardiol. 6, 122–127.
Heilbronn, L. K. and Ravussin, E. (2003). Am. J. Clin. Nutr. 78, 361–369.
Bodkin, N. L., Alexander, T. M., Ortmeyer, H. K., Johnson, E., and Hansen, B. C. (2003). J. Gerotol. A Biol. Sci. Med. Sci. 58, 212–219.
Wang, C., Weindruch, J. R., Fernandez, J. R., Coffey, C. S., Patel, P., and Allison, D. B. (2004). Int. J. Obesity Res. 28, 357–362.
Anson, R. M. (2004). Ann. NY Acad. Sci. 1019, 427–429.
Seshardi, S., Wolf, P. A., Beiser, L. J., et al. (2001). Arch. Internal Medicine 161, 2342–2350.
Van Den Buuse, M. (1994). Physiol. Behav. 55, 783–787.
von Eiff, A. W., Plotz, E. J., Beck, K. J., and Czernik, A. (1971). Am. J. Obstet. Gynecol. 109, 887–892.
Clark, J. T., Keaton, A. K., Sahu, A., Kalra, S. P., Mahajan, S. C., and Gudger, J. N. (1998). Regul. Peptides 75–76, 335–345.
Clark, J. T., Sahu, A., Mrotek, J. J. and Kalra, S. P. (1991). Am. J. Physiol. 261, R1234-R1241.
Clark, J. T. (1995). Neurosci. Biobehav. Rev. 19, 279–302.
Bunag, R. D. and Teravainen, T. L. (1991). Mech. Ageing Dev. 59, 197–213.
Hoeg, J. M., Willis, I. R., and Weinberger, M. H. (1977). Am. J. Physiol. 233, H369-H373.
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Clark, J.T., Chakraborty-Chatterjee, M., Hamblin, M. et al. Estrogen depletion differentially affects blood pressure depending on age in long-evans rats. Endocr 25, 173–186 (2004). https://doi.org/10.1385/ENDO:25:2:173
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DOI: https://doi.org/10.1385/ENDO:25:2:173