Estrogen depletion induces NaCl-sensitive hypertension  in female spontaneously hypertensive rats

Fang, Zhiwu; Carlson, Scott H.; Chen, Y. F.; Oparil, Suzanne; Wyss, J. Michael

doi:10.1152/ajpregu.2001.281.6.r1934

Cited by 62 publications

(57 citation statements)

References 41 publications

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“…However, there is evidence that certain 11␤HSD2 alleles are associated with increased salt sensitivity in humans (33), and it would be interesting to examine the BP of ArKO mice on a high salt diet. Studies in hypertensive rats show that a high salt diet does indeed increase MAP in ovariectomized rats and that this increase can be attenuated by phytoestrogens (34). The administration of sympathetic blockade restored arterial BPs to control levels in this study, suggesting that estrogen acts by attenuating sympathetic overactivity in response to a high salt diet.…”

Section: Discussionsupporting

confidence: 59%

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

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Obeyesekere

Jones³

et al. 2004

Endocrinology

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Aromatase-deficient (ArKO) mice are deficient in estrogens due to deletion of the aromatase gene. We hypothesized that there may be changes in the cardiovascular system of ArKO mice because of evidence linking estrogens with improved cardiovascular outcomes and the induction of the glucocorticoid-metabolizing enzyme, 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2), gene in the kidney, which is important for the regulation of blood pressure (BP). BP and baroreflex sensitivity (BRS) in female conscious ArKO mice were compared with those in age-and weight-matched wild-type (WT) mice. Power spectral analysis was used to determine cardiovascular variability and BRS. Although systolic BP was similar in the two groups, diastolic and mean BPs were lower in the ArKO mice (؊6.3 ؎ 1.9 and ؊4.6 ؎ 2.1 mm Hg, respectively).Heart rate (HR) was greater in the ArKO mice (؉36 ؎ 6 beats/ min). The mean BP in WT mice was 105 mm Hg, and the HR was 481 beats/min. In the autonomic frequency range, BP variability was 74% greater, and HR variability was only 26% that in WT mice. The BRS of ArKO mice was 46% of the value observed in WT mice. 11␤HSD2 levels were unaltered in ArKO mice, except in the kidney, where they were only 10% of WT levels. Estradiol administration to ArKO mice restored renal 11␤HSD2 to WT levels. The results show that ArKO mice have lower diastolic BP, but increased BP variability, perhaps due to an impaired BRS. Thus, aromatase activity is critical for normal autonomic control of the heart and, hence, for reducing the deleterious effects of high BP variability. (Endocrinology 145: 4286 -4291, 2004)

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Section: Discussionsupporting

confidence: 59%

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Head

Obeyesekere

Jones³

et al. 2004

Endocrinology

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“…In 3-month-old female SHR, dietary NaCl excess causes a modest rise in arterial pressure (Ϸ10 mm Hg), but chronic estrogen depletion greatly exacerbates the hypertensive response to a high NaCl diet (Ͼ40 mm Hg). 11 Compared with these data from young SHR, the current data indicate that estrogen is much less protective in older SHR. Whereas the NaCl-induced rise in arterial pressure in the estrogen-depleted SHR in the current study is Ϸ50 mm Hg, the rise in the estrogen-replete (intact) and the estrogen-treated groups is nearly 40 mm Hg (Figure 1).…”

Section: Discussioncontrasting

confidence: 54%

“…Renal function is impaired in SHR, and this may contribute importantly to potential sodium and volume loading in the high NaCl-fed rats. 35 Also, our preliminary study indicates that the elimination of phytoestrogens from the diet of male SHR increases their hypertensive response to a high NaCl diet by a sympathetic nervous system mechanism, 36 thus suggesting that phytoestrogens are protective in male SHR.…”

Section: Discussionmentioning

confidence: 80%

“…Our studies in spontaneously hypertensive rats (SHR) demonstrate that young female SHR (compared with age-matched male SHR) have a lower arterial pressure and a reduced hypertensive response to excess dietary NaCl. 11 Elimination of most endogenous estrogen by ovariectomy causes no significant change in arterial pressure and only a modest alteration in NaCl-sensitive hypertension. However, simultaneous removal of both endogenous and dietary estrogens (phytoestrogens in soy-based rodent chow) leads to a small rise in baseline arterial pressure and a very large increase in the hypertensive response to a high NaCl diet.…”

mentioning

confidence: 99%

“…However, simultaneous removal of both endogenous and dietary estrogens (phytoestrogens in soy-based rodent chow) leads to a small rise in baseline arterial pressure and a very large increase in the hypertensive response to a high NaCl diet. 11 Further, in male SHR, a high NaCl diet activates the sympathetic nervous system and, thereby, increases arterial pressure. 12,13 A key gender difference in the response to the dietary NaCl excess is that in male (but not female) SHR, the high NaCl diet decreases norepinephrine release in an important sympatho-inhibitory nucleus, the anterior hypothalamic nucleus (AHN).…”

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confidence: 99%

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Estrogen Depletion Increases Blood Pressure and Hypothalamic Norepinephrine in Middle-Aged Spontaneously Hypertensive Rats

et al. 2003

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Abstract-In male spontaneously hypertensive rats (SHR) a high NaCl diet increases arterial pressure via a reduction in anterior hypothalamic nucleus norepinephrine release. Young female SHR are relatively well protected from this NaCl-sensitive hypertension, but depletion of both endogenous and dietary estrogens greatly exacerbates NaCl-sensitive hypertension. This study tests the hypothesis that estrogen also protects late middle-aged female SHR from NaCl-sensitive hypertension and that this effect is mediated by an estrogen-related effect on hypothalamic norepinephrine release. Ten-month-old female SHR were ovariectomized and placed on a phytoestrogen-free diet containing either basal or high NaCl. Each rat was implanted with a silastic tube containing 17␤ estradiol or vehicle. Three months later, arterial pressure and hypothalamic norepinephrine metabolite levels (MOPEG) were measured. On the basal NaCl diet, estrogen-depleted rats displayed increased arterial pressure (12 mm Hg) and decreased anterior hypothalamic nucleus MOPEG (20%). Both effects were reversed by estrogen treatment. In all groups, the high NaCl diet increased arterial pressure by over 35 mm Hg and reduced anterior hypothalamic nucleus MOPEG by Ͼ60%. Across all groups, there was a significant inverse correlation between arterial pressure and anterior hypothalamic nucleus MOPEG. These data suggest that both dietary NaCl excess and estrogen depletion raise arterial pressure in middle-aged female SHR by a decreasing hypothalamic norepinephrine. Key Words: estrogen Ⅲ norepinephrine Ⅲ sodium Ⅲ sympathetic nervous system Ⅲ blood pressure H ypertension significantly contributes to premature death in the fastest-growing segment of the population, ie, adults over 65 years of age. 1 The incidence of hypertension in this age group is about 60%. [2][3][4] Further, between 30% and 50% of hypertensive patients are NaCl-sensitive, ie, they display a significant (Ͼ10%) increase in blood pressure when placed on a high NaCl diet (200 to 250 mEq Na ϩ /d for 7 days). The NaCl-sensitive hypertensive patients, in contrast to normotensive and NaCl-resistant hypertensive subjects, fail to suppress plasma norepinephrine (NE) after the ingestion of a diet high in NaCl. 5,6 These and other studies suggest that the sympathetic nervous system contributes importantly to NaCl-sensitive hypertension in aging humans. 7,8 Several lines of evidence indicate that, compared with men, premenopausal women have a lower rate of hypertension. After menopause this relative protection appears to be lost, and women experience a rapid rise in hypertension (including salt-sensitive hypertension). 9,10 This increase appears to be related to the menopausal loss of estrogen. Our studies in spontaneously hypertensive rats (SHR) demonstrate that young female SHR (compared with age-matched male SHR) have a lower arterial pressure and a reduced hypertensive response to excess dietary NaCl. 11 Elimination of most endogenous estrogen by ovariectomy causes no significant change in arterial pressur...

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The Anterior Hypothalamus and Salt-Sensitive Hypertension

Oparil

Wyss

2004

Neural Mechanisms of Cardiovascular Regulation

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Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats

Cited by 62 publications

References 41 publications

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Estrogen Depletion Increases Blood Pressure and Hypothalamic Norepinephrine in Middle-Aged Spontaneously Hypertensive Rats

The Anterior Hypothalamus and Salt-Sensitive Hypertension

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