Abnormalities of hippocampus and hypothalamus are commonly observed in rats with genetic (SHR) or
mineralocorticoid/
salt-induced
hypertension. In the hippocampus, changes include decreased cell proliferation in the dentate gyrus (DG),
astrogliosis and decreased neuronal density in the hilus, whereas in the hypothalamus expression of
arginine vasopressin (AVP) is markedly elevated. Here, we report that
estradiol treatment overturns these abnormalities. We used 16-week-old male SHR with blood pressure (BP) approximately 190 mmHg and their normotensive Wistar-Kyoto (WKY) controls, and male Sprague-Dawley rats made hypertensive by administration of 10mg
deoxycorticosterone acetate (
DOCA) every other day plus 1% NaCl as drinking fluid for 4 weeks (BP approximately 160 mmHg). Controls received oil vehicle plus 1% NaCl only. Half of the animals in each group were implanted s.c. with a single
estradiol benzoate pellet weighing 14 mg for 2 weeks.
Estradiol-treated SHR and
DOCA-
salt rats showed, in comparison to their respective
steroid-free groups: (a) enhanced proliferation in the DG measured by
bromodeoxyuridine incorporation; (b) decreased number of
glial fibrillary acidic protein (GFAP) immunopositive astrocytes; (c) increased density of neurons in the hilus of the DG, and (d) decreased hypothalamic AVP
mRNA expression. These results indicate that neuronal and glial alterations of hypertensive models are
plastic events reversible by
steroid treatment. The
estradiol protective effects may be of pharmacological interest to attenuate the consequences of
hypertensive encephalopathy.