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Sex Steroids and Gender in Cardiovascular-Renal Physiology and Pathophysiology

Effect of dietary sodium on estrogen regulation of blood pressure in Dahl salt-sensitive rats

Center for the Study of Sex Differences in Health, Aging and Disease, Georgetown University, Washington, District of Columbia

Submitted 11 November 2007 ; accepted in final form 29 January 2008

The effects of high-sodium (HS) and normal-sodium (NS) diets on ovarian hormone modulation of mean arterial pressure (MAP) were examined in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Ovariectomy increased MAP (OVX-Sham) to a greater extent in DS rats maintained for 2 wk on a HS (22 mmHg) compared with a NS (6 mmHg) diet. Ovariectomy had no effect on MAP in DR rats on NS but did increase MAP in rats on HS (10 mmHg) diets. On HS diets, glomerular filtration rate (GFR) was 36% less in the DS-Sham than DR-Sham animals; ovariectomy increased GFR in both strains by 1.4–1.5-fold; glomerular angiotensin II type 1 receptor (AT₁R) densities were 1.6-fold higher in the DS-Sham than in the DR-Sham group; ovariectomy increased glomerular AT₁R densities by 1.3-fold in DR rats but had no effect in DS rats; 17β-estradiol (E₂) downregulated adrenal AT₁R densities in both strains on either diet; ovariectomy reduced estrogen receptor- (ER-) protein expression in the renal cortex by 40–50% although renal ER- expression was 34% lower in DS than in DR rats. These observed effects of gonadectomy were prevented by E₂ treatment, suggesting that E₂ deficiency mediates the effects of ovariectomy on MAP, GFR, AT₁R densities, and renal ER- protein expression. In conclusion, ovariectomy-induced increases in MAP are augmented by HS diet in both strains, and this effect is not mediated by a reduction in GFR. Aberrant renal AT₁R regulation and reduced renal ER- expression are potential contributors to the hypertensive effects of E₂ deficiency in DS rats. These findings have implications for women with salt-sensitive hypertension and women who are E₂ deficient, such as postmenopausal women.

17β-estradiol; estrogen receptors; angiotensin II type 1 receptors; kidney; adrenal