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

Abstract

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 (AT(1)R) densities were 1.6-fold higher in the DS-Sham than in the DR-Sham group; ovariectomy increased glomerular AT(1)R densities by 1.3-fold in DR rats but had no effect in DS rats; 17beta-estradiol (E(2)) downregulated adrenal AT(1)R densities in both strains on either diet; ovariectomy reduced estrogen receptor-alpha (ER-alpha) protein expression in the renal cortex by 40-50% although renal ER-alpha expression was 34% lower in DS than in DR rats. These observed effects of gonadectomy were prevented by E(2) treatment, suggesting that E(2) deficiency mediates the effects of ovariectomy on MAP, GFR, AT(1)R densities, and renal ER-alpha 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 AT(1)R regulation and reduced renal ER-alpha expression are potential contributors to the hypertensive effects of E(2) deficiency in DS rats. These findings have implications for women with salt-sensitive hypertension and women who are E(2) deficient, such as postmenopausal women.

Female sex hormones protect against salt-sensitive hypertension but not essential hypertension

“…Female sex hormones have been widely suggested to protect against cardiovascular disease and the development of salt sensitivity in premenopausal women and experimental animals (35,40). Consistent with previous reports in the literature, OVX increased basal BP in female DS rats but not in SHR (12,15,59). Initiation of a HS diet increased BP in both strains, although as expected, DS had a faster and more pronounced increase in BP than SHR.…”

“…Relative to SHR, DS rats have been suggested to be an NO-deficient rat strain (1,4,59), although few studies have directly compared NOS in the two strains. On the basis of these data, we hypothesized that female SHR would have a greater increase in renal inner medullary NOS in response to a HS diet compared with DS rats.…”

“…Among women, the prevalence of salt sensitivity increases following both surgical and natural menopause (14,38), suggesting that the loss of ovarian hormones renders women prone to salt sensitivity and increases their risk of developing hypertension (38). This is further supported by studies in experimental animals; surgical ovariectomy (OVX) increases the BP response to salt in many rat strains, including Dahl salt-sensitive (DS) and Dahl salt-resistant rats (59), mRen (2).Lewis rats (7), Sprague-Dawley rats treated with aldosterone (57), and spontaneously hypertensive rats (SHR) (10). These data suggest that female sex hormones are critical in influencing sodium handling and BP regulation; however, the mechanisms responsible continue to be investigated.…”

“…Therefore, additional studies tested the hypothesis that blunted increases in BP in female SHR will be accompanied by an increase in renal inner medullary NOS activity and expression in response to a HS diet, which will not be evident in female DS rats. OVX increases BP in female DS rats, even when maintained on a normal salt diet (12,15,59). In contrast, BP in female SHR tends to be resistant to OVXmediated alterations in BP (12, 49).…”

“…There is ample evidence in the literature supporting a role for increased ANG II and AT 1 receptor activation in female experimental animals following ovariectomy or high-salt diet that is blocked by estrogen supplementation (12,15,39,59). However, less is known regarding the role of the NO/NOS pathway in females following a high-salt diet, despite the fact that numerous studies have suggested that one of the primary mechanisms underlying the cardiovascular protective effect of estrogen is via increased NO production (31).…”