Chronic Estradiol Treatment Decreases Angiotensin II Receptor Density in the Anterior Pituitary Gland and Adrenal Cortex but Not in the Mesenteric Artery

Carrière, Paul D.; Léan, André De; Gutkowska, Jolanta; Genest, Jacques; Cantin, M.

doi:10.1159/000124508

Cited by 31 publications

(17 citation statements)

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“…Female sex hormones can diminish the vasoconstrictor effects of angiotensin II 22 and downregulate vascular angiotensin II receptors. 23 Recent studies by Brosnihan et al 24 have led to the proposal that female sex hormones can shift the direction of the vasoconstrictor-vasodilator balance of the renin-angiotensin system by reducing the formation of the vasoconstrictor (angiotensin II) while increasing the formation of the vasodilator (angiotensin). [1][2][3][4][5][6][7] The development of hypertension in OVX females maintained on a low-sodium diet may be related to activation of the renin-angiotensin system.…”

Section: Discussionmentioning

confidence: 99%

Role of Female Sex Hormones in the Development and Reversal of Dahl Hypertension

2000

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Abstract-Female sex hormones protect against the development of Dahl hypertension mediated by increases in dietary sodium. The role of female sex hormones in the reversal of Dahl hypertension mediated by decreases in dietary sodium is unknown. The goal of this study was to identify sex differences in the reversal of Dahl hypertension and the associated changes in water and electrolyte homeostasis. Male (M, nϭ8), female (F, nϭ8), and ovariectomized female (OVX, nϭ9) Dahl salt-sensitive rats were instrumented with an abdominal radiotelemetry device for 24-hour monitoring of blood pressure (BP) and heart rate. Daily measurements of food intake, water intake, and urine output were recorded as diet was changed from a low-sodium diet (0.15% NaCl) to a diet containing 8% NaCl. The diet was then changed back to 0.15% NaCl. The responses to changes in the salt diet were compared with responses observed in rats (M, nϭ4; F, nϭ4; OVX, nϭ4) that were maintained on 0.15% NaCl during the experiment. Sex differences in BP were observed when M, F, and OVX rats were fed 8% NaCl diet for 2 weeks (152Ϯ4, 141Ϯ3, and 154Ϯ5 mm Hg, respectively). BP was significantly greater (PϽ0.05) in M and OVX rats than in F rats. Fluid balance (water intake minus urine volume) and sodium balance (sodium intake minus sodium excretion) were similar in all groups on the 8% NaCl diet. BP in time-control M, F, and OVX rats was 121Ϯ3, 130Ϯ4, and 162Ϯ11 mm Hg, respectively. Compared with time-control groups, differences in BP while rats were eating the 8% NaCl diet were observed in M and F rats but not OVX rats.Reinstatement of an NaCl-deficient diet reversed the hypertension in M and F but not OVX rats (124Ϯ4, 124Ϯ2, and 145Ϯ5 mm Hg, respectively). The changes in dietary sodium caused similar changes in renal handling of sodium and water in all groups of rats; therefore, the effect on blood pressure was independent of renal excretory function. The inability to reverse the hypertension by decreasing sodium intake in OVX rats and the development of spontaneous hypertension in OVX females maintained on a low-sodium diet indicates that removal of the female sex hormones predisposes the animal to the development of hypertension that is sodium independent. We conclude that female sex hormones protect Dahl S rats against the development of sodium-dependent and -independent hypertension. Key Words: hypertension, sodium-dependent Ⅲ salt sensitivity Ⅲ hormones T he relationship between salt intake and blood pressure has been extensively studied in humans and provides clear evidence that a subpopulation of humans are sensitive to alterations in salt intake. Salt sensitivity is usually identified by a reduction in blood pressure (5% to 10%) in response to a decrease in sodium intake or a rise in blood pressure (5% to 10%) in response to an increase in sodium intake. 1 Although the prevalence of hypertension in premenopausal women is lower than in men of the same age, the incidence of hypertension in women doubles after menopause, 2 which suggests that female sex hor...

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Section: Discussionmentioning

confidence: 99%

Role of Female Sex Hormones in the Development and Reversal of Dahl Hypertension

2000

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“…9 Estrogen has been shown to suppress the renin-angiotensin system (RAS) by decreasing angiotensin-converting enzyme activity in several tissues, 10 -12 and we have found that estrogen decreases Ang II levels in the adrenal. 5 Estrogen also reduces the number of AT 1 receptors in the adrenal cortex, 13,14 pituitary gland, 13,15 and kidney. 16 Furthermore, we and others have shown that estrogen reduces tissue responsiveness to Ang II.…”

Section: Hinojosa-laborde Et Al Estrogen and Aging In Dahl Salt-sensimentioning

confidence: 98%

Ovariectomy Augments Hypertension in Aging Female Dahl Salt-Sensitive Rats

et al. 2004

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Abstract-The ovariectomized (OVX) Dahl salt-sensitive (DS) rat fed a low-salt diet is a model of postmenopausal hypertension. In addition to estrogen loss, aging can also contribute to postmenopausal hypertension. We hypothesized that: (1) female DS rats on a low-salt diet become hypertensive with age; (2) ovariectomy accelerates age-dependent hypertension in the DS rat caused by estrogen depletion; and (3) this hypertension correlates with increased type 1 angiotensin receptor (AT 1 R) number (Bmax). Blood pressure was monitored by telemetry from 3 to 12 months and AT 1 R Bmax was determined by Scatchard analysis in glomeruli and adrenal cortex. Three groups of DS rats were studied: intact, OVX, and 17␤-estradiol-replaced OVX (OVXϩE). In intact rats, aging to 12 months resulted in hypertension (159Ϯ6 mm Hg) and an 82% decrease in estrogen. Blood pressure in OVX was significantly higher than OVXϩE through 12 months of age (173Ϯ4 versus 150Ϯ8 mm Hg). At 4 months, OVX increased AT 1 R Bmax compared with intact and OVXϩE in both glomeruli and adrenal cortex. Aging also increased AT 1 R Bmax in these tissues in intact rats. In summary, female DS rats fed a low-salt diet have hypertension develop with age, that is accelerated by OVX and attenuated by estrogen replacement. Concurrently, AT 1 Rs are upregulated by age and OVX, which is prevented by estrogen replacement. This study suggests that an increased activity of the renin angiotensin system contributes to the development of hypertension, and estrogen protects against this process. Key Words: aging Ⅲ Dahl rats Ⅲ hypertension, sodium-dependent Ⅲ estrogen Ⅲ renin-angiotensin system T he prevalence of hypertension in premenopausal women is lower compared with men of the same age. 1 After menopause, the incidence of hypertension in women doubles and becomes similar to men, suggesting that the loss of female gonadal steroids caused by menopause are a risk factor for postmenopausal hypertension. 2 In addition, there is evidence that salt-sensitivity also contributes to postmenopausal hypertension. 3 The mechanisms of postmenopausal hypertension are not well-understood and few animal models exist to study this phenomenon. We have shown that adult (4 months) female normotensive Dahl salt-sensitive (DS) rats maintained on a low-salt (LS) diet become hypertensive after ovariectomy (OVX). 4 Thus, the ovariectomized DS rat serves as an experimental model of postmenopausal hypertension. Furthermore, this is the first animal model in which OVX results in spontaneous hypertension. These studies suggest that salt-sensitive premenopausal women may be protected against the development of hypertension because of the presence of female gonadal steroids and that after menopause, the protective effects of these hormones are lost, thus contributing to the development of hypertension. Although these observations implicate a role for estrogen (E), the effects of aging on the regulation of blood pressure could also contribute to the development of salt-sensitive hypertension in postmenopa...

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“…Chronic estrogen treatment is known to modify Ang II receptor density in the adrenal cortex and pituitary. 27,28 In addition to its endocrine actions, estrogen may exert its beneficial effect as a vasodilator, primarily acting through effects on the endothelium. Estrogen enhances vascular relaxation in the forearm and coronary beds in postmenopausal women.…”

Section: Fisher Et Al Adrenal Response In Black Hypertensionmentioning

confidence: 99%

Adrenal Response to Angiotensin II in Black Hypertension

Fisher

Hurwitz²,

Jeunemaı̂tre³

et al. 2001

Hypertension

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Abstract-Adrenal responsiveness to angiotensin (Ang) II is markedly blunted in black hypertensive patients compared with white hypertensive patients. One characteristic of this blunted adrenal response in whites is a powerful sexual dimorphism: premenopausal white women rarely show blunted responses. This abnormality, most evident when the system is activated by a low-salt diet, is a cardinal feature of the syndrome of nonmodulation, affecting a large percentage of white hypertensive patients. Nonmodulation is also marked by an increase in cardiovascular risk beyond that from hypertension itself. This study investigated whether young black women are likewise spared its expression or whether the adrenal unresponsiveness common among black hypertensive patients is unaccompanied by a gender bias. We compared the adrenal response to Ang II in 382 hypertensive patients (313 white, 69 black; 238 male, 144 female). Ang II was infused when subjects were in balance on a 10-mmol Na ϩ intake. As anticipated, white hypertensive patients showed a very strong sexual dimorphism, with women having twice the aldosterone response of men (Pϭ0.0001). Blacks, on the other hand, showed no gender difference (Pϭ0.9). Increasing age had the dramatic effect of reducing responsiveness in white women but not in blacks. Young black women demonstrated the same blunting of adrenal responsiveness as older black women and black men of all ages. Mechanisms protecting against a blunted adrenal response to Ang II in young white women are absent in blacks. These differences may contribute to the markedly increased prevalence of hypertension in young black women. Key Words: angiotensin II Ⅲ race Ⅲ gender Ⅲ aldosterone Ⅲ potassium Ⅲ hypertension, renal W e have reported a striking frequency of blunted adrenal responses to angiotensin (Ang) II infusion in black hypertensive patients. 1 Blunting of the adrenal response to Ang II is a cardinal feature of the syndrome of nonmodulation (NM). One additional characteristic of this response in NM is a powerful sexual dimorphism: premenopausal white women rarely show a blunted adrenal response. 2 NM is also marked by an increase in cardiovascular risk factors and cardiovascular risk itself. 3,4 Young black women have up to 3 times the risk for coronary heart disease and death of white women. 5,6 A large degree of this excess risk is attributable to differences in coronary risk factors, including elevated blood pressure. 7,8 This striking racial difference in risk has not been observed among men.Prompted by these observations, we undertook a systematic analysis of adrenal responsiveness in a large cohort of black and white hypertensive patients to test the hypothesis that the sexual dimorphism protecting young white women from phenotypic expression of NM is not present among blacks. The finding that black women have a significantly greater frequency of a blunted adrenal response to Ang II than do young white women may help explain their dramatic increase in cardiovascular risk. MethodsThe data reported in the ...

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Chronic Estradiol Treatment Decreases Angiotensin II Receptor Density in the Anterior Pituitary Gland and Adrenal Cortex but Not in the Mesenteric Artery

Cited by 31 publications

References 25 publications

Role of Female Sex Hormones in the Development and Reversal of Dahl Hypertension

Role of Female Sex Hormones in the Development and Reversal of Dahl Hypertension

Ovariectomy Augments Hypertension in Aging Female Dahl Salt-Sensitive Rats

Adrenal Response to Angiotensin II in Black Hypertension

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