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Hypertension. 2004;43:918-923
Published online before print March 15, 2004, doi: 10.1161/01.HYP.0000124670.03674.15
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(Hypertension. 2004;43:918.)
© 2004 American Heart Association, Inc.


Brief Reviews

Novel Mechanisms Responsible for Postmenopausal Hypertension

Jane F. Reckelhoff; Lourdes A. Fortepiani

From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.

Correspondence to Dr Jane F. Reckelhoff, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216. E-mail jreckelhoff{at}physiology.umsmed.edu


*    Abstract
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*Abstract
down arrowIntroduction
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down arrowCharacterization of the...
down arrowPossible Mechanisms Responsible...
down arrowDoes Oxidative Stress Play...
down arrowDoes Endothelin Play a...
down arrowDoes the RAS Play...
down arrowDoes Obesity Play a...
down arrowDoes Activation of the...
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down arrowReferences
 
Blood pressure increases in many women after menopause. Hypertension is one of the major risk factors for cardiovascular disease. However, the mechanisms responsible for the postmenopausal increase in blood pressure are yet to be elucidated. Various humoral systems have been proposed to play a role in postmenopausal hypertension, such as changes in estrogen/androgen ratios, increases in endothelin and oxidative stress, and activation of the renin-angiotensin system (RAS). In addition, obesity, type II diabetes, and activation of the sympathetic nervous system are common in postmenopausal women and may also play important roles. However, progress in elucidating the mechanisms responsible for postmenopausal hypertension has been hampered by the lack of a suitable animal model. The aging female spontaneously hypertensive rat (SHR) exhibits many of the characteristics found in postmenopausal women. In this review, some of the possible mechanisms that could play a role in postmenopausal hypertension are discussed, as well as the characteristics of the aged female SHR as a model to study.


Key Words: endothelin • renin-angiotensin system • oxidative stress • obesity • diabetes mellitus • sympathetic nervous system


*    Introduction
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Before menopause, blood pressure is typically lower in women than in age-matched men.1 In aging men and women, systolic and diastolic blood pressures increase, although in later years the diastolic plateaus or even declines.1–3 However, in postmenopausal women, the prevalence of hypertension and cardiovascular disease risk increases regardless of ethnic origin. Results from the National Health and Nutrition Examination Survey (NHANES III) showed that in Hispanic women and non-Hispanic black women, the prevalence of hypertension was similar to, or higher than, that in men by age 60 years.4 In non-Hispanic white populations, the prevalence of hypertension was higher in women than in men by age 70 years.4 The increase in blood pressure in postmenopausal women does not occur as soon as the ovary becomes senescent, but rather over a number of years.5 The mechanisms responsible for the increased blood pressure in women after menopause are not known. This review focuses on the use of the spontaneously hypertensive rat as a model of postmenopausal hypertension and evaluates the possible mechanistic roles of the sex hormones, oxidative stress, endothelin, renin-angiotensin system (RAS), weight gain, and sympathetic activation in postmenopausal hypertension.


*    Animal Model for the Study of Postmenopausal Hypertension
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The elucidation of mechanisms responsible for postmenopausal hypertension has been stunted by lack of an animal model. Sheep, rabbits, nonhuman primates, rats, and mice have been used as models of various menopausal changes;6 however, to our knowledge, there is no animal model of naturally occurring postmenopausal hypertension. There have been attempts to mimic menopause by ovariectomizing animals;7,8 however, these have rarely taken into account the effect of aging and cessation of ovarian function. In any case, there is no normotensive animal model that exhibits hypertension with aging.

Female spontaneously hypertensive rats (SHR) stop cycling at age 10 to 12 months and have low estradiol levels comparable to postmenopausal women.9 As shown in Figure 1, in younger SHR (ages 4 and 8 months), females have lower blood pressure than males.6,9,10 However, by age 16 to 18 months, the blood pressure has increased by 25 to 35 mm Hg, compared with young females, and 15 mm Hg when compared with 8-month-old females. In addition, the sex difference in blood pressure no longer exists because of the increase in blood pressure in old females, whereas blood pressure in male SHR remains fairly stable after age 8 months.9,11



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Figure 1. Mean arterial pressure increases with age in post- cycling female SHR. Blood pressures were measured in male and female SHR via femoral catheters at various ages. *P<0.01, compared with females of same age; {ddagger}P<0.05, compared with females of young ages. Data are redrawn from Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003;41:640–645.

Another hypertensive rat strain that also exhibits increases in blood pressure with aging is the Dahl salt-sensitive rat. Even when fed a low-salt diet, blood pressure increases with time in males and females. If young female Dahl rats are ovariectomized and fed a high-salt diet, the blood pressure increases to higher levels than in intact females.12 At what age these animals cease cycling and what happens to their blood pressure after cessation of cycling have not been determined, to our knowledge.

In addition to the rat models of postmenopausal hypertension, the follicular-stimulating hormone receptor knockout mouse has been developed and also exhibits some of the characteristics of postmenopausal women.13 These animals have low plasma estradiol levels, hypertension when compared with their wild-type counterparts, hypercholesterolemia, and weight gain.13 However, when studied at age 14 to 16 weeks, these animals did not exhibit increased oxidative stress or endothelial dysfunction, factors common to postmenopausal women.13


*    Characterization of the Postcycling SHR as a Model of Postmenopausal Hypertension
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In addition to reduced levels of estradiol after cessation of cycling, the old female SHR (postmenopausal rat [PMR]), aged 18 months, exhibits a 4-fold increase in serum testosterone compared with young females, aged 4 months (Figure 2).9 Some of this increase is age-related, however, because female SHRs that were ovariectomized at age 9 months also had an increase in serum testosterone at age 18 months, but had no further increase in blood pressure after age 8 months.9



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Figure 2. Serum free-testosterone increases with age in naturally postcycling female SHR and ovariectomized female SHR. Studies were performed in young (4 months) and old (18 months) rats. Some rats were ovariectomized at age 8 months. *P<0.05, compared with young females; {ddagger}P<0.05 compared with old ovariectomized females.

Along with the increase in blood pressure with age, the PMR also has a reduction in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance compared with the less hypertensive ovariectomized females of the same age or when compared with young females (Figure 3).9 PMRs also excrete significantly more protein than do young females (Figure 4). When morphology of the kidneys was performed, there was a significant increase in the percentage of glomeruli that exhibit some level of sclerosis compared with ovariectomized females of the same age that exhibit no injury (Reckelhoff and Racusen, unpublished data, 2002).



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Figure 3. Renal function decreases and renal vascular resistance increases in postcycling female SHR. Changes in glomerular filtration rate (A), renal plasma flow (B), and renal vascular resistance with age in female SHR, aged 4 or 18 months, or females that were ovariectomized at age 9 months and studied at 18 months (ovx-18 months). *P<0.001, compared with females, aged 4 months; {ddagger}P<0.05, compared with old ovariectomized females. Data are redrawn from Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003;41:640–645.



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Figure 4. Urinary protein excretion increases with age in female SHR. *P<0.001, compared with females, age 4 months. Data redrawn from Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003;41:640–645.

Plasma renin activity (PRA) has been reported to be increased in some postmenopausal women.14,15 The PMR also has an increase in PRA compared with young females (Figure 5). In contrast, in the aging male SHR, the PRA decreases such that the PRAs are similar in old males and females.9



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Figure 5. PRA increases with age in postcycling female SHR. PRA was measured in female SHR, age 4 or 18 months. *P<0.01, compared with females, aged 4 months. Data are redrawn from Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003;41:640–645.

Oxidative stress is also increased in kidneys and plasma of PMRs. As shown in Figure 6, plasma F2-isoprostanes were significantly increased in PMRs compared with young females.9 Furthermore, treatment of PMRs with vitamins E and C for 8 months, beginning before cessation of cycling, reduced oxidative stress (as measured by reduction in urinary excretion rates of F2-isoprostanes) and prevented the blood pressure increase (Figure 7).9 In old males SHRs, however, vitamins E and C had no effect on blood pressure. Thus, the PMR exhibit many of the characteristics found in postmenopausal women.



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Figure 6. Plasma F2-isoprostanes increase with age in post- cycling female SHR, age 4 or 18 months. *P<0.0001, compared with females, aged 4 months. Data are drawn from Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003;41:640–645.



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Figure 7. Chronic treatment with antioxidant vitamins reduces blood pressure in postcycling female SHR. Male and female SHR were administered vitamins E (5000 IU/kg diet) and C (100 mg/L drinking water) or vehicles for 8 months, beginning when they were age 8 months. *P<0.01, compared with untreated rats. Data are drawn from Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003;41:640–645.


*    Possible Mechanisms Responsible for Postmenopausal Hypertension: Do Changes in Estrogen/Androgen Ratios Play a Role in Postmenopausal Hypertension?
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Experimentally, estradiol has a variety of effects that should be cardiovascular-protective,16–18 but many of these studies were performed in vitro. However, despite these positive results, hormone replacement therapy (HRT) has not been shown to consistently lower blood pressure in postmenopausal women. As determined by 24-hour ambulatory blood pressure monitoring, HRT typically resulted in changes of only 3 to 4 mm Hg, some at night only, some during the day only.19–22 The mode of delivery of HRT, whether oral or transdermal, may play a role in its efficacy, but the data are not consistent with which delivery mode is more effective.20,22 Many of these studies were short-term, ie, <1 year. In contrast, Prelevic et al studied healthy postmenopausal women who had been using HRT for at least 5 years and found that HRT had either no effect or increased blood pressure.23 Similar findings were reported from the Women’s Health Initiative study, a 5-year study in which HRT increased systolic blood pressure.24 Proponents of the beneficial role of estradiol in cardiovascular disease cite the use of progesterone in HRT as possibly negating the positive effects of estradiol.16 However, in women who have experienced surgical menopause, estrogen replacement therapy also did not result in significant sustained reductions in blood pressure.25,26 Further information regarding the efficacy of estrogen treatment alone may come out of the "estrogen only" arm of the Women’s Health Initiative study that is still underway at this writing.24

A relative hyperandrogenic state may play a role in postmenopausal hypertension;27,28 however, whether androgens are changed in postmenopausal women is still controversial. The conventional wisdom is that androgen levels, like estrogen, decrease with age in men and women. However, Jiroutek et al29 reported that women who were followed for 10 years after cessation of cycling had increases in serum testosterone but decreases in dihydrotestosterone. Similarly, in the Rancho Bernardo cohort, Laughlin et al reported that serum testosterone decreased at first after menopause, but increased with age thereafter, reaching premenopausal levels by age 70 to 79 years.30 As mentioned, the postcycling SHR has a 4-fold increase in serum testosterone compared with young females, consistent with increases in serum testosterone in postmenopausal women.9

Therefore, an increase in androgens could play a role in causing postmenopausal hypertension. In support of this hypothesis, premenopausal women with polycystic ovary syndrome or virilizing tumors have elevated serum androgens and increases in blood pressure.31–33 There are several ways in which androgens could impact blood pressure. Testosterone supplementation in rats stimulates production of angiotensinogen, the substrate for renin, in the kidney, activating the RAS.34,35 Androgen supplementation in women is also associated with increased plasma endothelin.36 In addition, supplementation of dihydrotestosterone (10–9 M) in cultured mesangial cells from SHR causes an increase in oxidative stress and increases angiotensin type-1 (AT1) receptor expression (Cucchiarelli and Reckelhoff, unpublished data, 2003). Thus, androgens could play a role in postmenopausal hypertension by affecting the RAS, endothelin, or oxidative stress.


*    Does Oxidative Stress Play a Role in Postmenopausal Hypertension?
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In postmenopausal women, oxidative stress increases, and the longer the time since menopause occurred, the more oxidative stress that is present.37,38 Furthermore, plasma glutathione peroxidase is reduced, whereas levels of superoxide dismutase are either unchanged or significantly increased.37 As mentioned and as shown in Figure 7, PMR have an increase in oxidative stress, and long-term treatment with vitamins E and C reduces blood pressure,9 supporting a role for oxidative stress in mediating postmenopausal hypertension in the SHR.


*    Does Endothelin Play a Role in Postmenopausal Hypertension?
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Endothelin is a potent vasoconstrictor that, when administered on a long-term basis, causes increases in sodium reabsorption in the kidney39 and increases blood pressure.39,40 Endothelin also stimulates oxidative stress by causing upregulation of the subunits of NAD(P)H oxidase and increasing superoxide.41 In postmenopausal women, plasma endothelin levels have been shown to be increased.42 In PMR, preproendothelin mRNA levels in the kidney are also increased compared with premenopausal female SHR (Yanes et al, unpublished data, 2003). In addition, long-term blockade of the endothelin ETA receptor reduces blood pressure in PMR to levels found in young females. This is unlike young females or old or young male SHR in which ETA receptor antagonism does not affect blood pressure.43,44 Thus, endothelin could be playing a role in postmenopausal hypertension in the PMR.

Why plasma endothelin increases in postmenopausal women is not clear. Estradiol inhibits endothelin synthesis.45,46 Thus, after menopause, this inhibitory effect would be lost. Endothelin synthesis can be upregulated by Ang II,47 and ETA receptors have been shown to mediate Ang II hypertension in animal studies.48,49 Testosterone treatment of women also increases plasma endothelin levels.36 Just as endothelin can cause oxidative stress, endothelin also increases in response to oxidative stress.50 Therefore, endothelin could be increased in postmenopausal women because of reductions in estradiol and increases in Ang II, oxidative stress, or androgens.


*    Does the RAS Play a Role in Postmenopausal Hypertension?
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It is commonly thought that PRA, and therefore the activity of the RAS, decreases with age in humans and animals. However, in men and women who had PRA measured serially for 9 years, PRA was higher in postmenopausal women than premenopausal women.14,15 PRA is also increased in PMR at age 18 months.9 Furthermore, treatment of PMR with losartan, an AT1 receptor antagonist, normalizes their blood pressure (Yanes and Reckelhoff, unpublished data, 2004).

The RAS plays a major role in control of blood pressure and body fluid volume (ie, pressure natriuresis).51 Ang II could also impact blood pressure in postmenopausal women by stimulating synthesis of preproendothelin47 or by producing oxidative stress.52,53 Thus, activation of the RAS not only may cause direct increases in blood pressure but also may stimulate endothelin and oxidative stress to further increase blood pressure in postmenopausal women and rats.

The ovary also has a distinct RAS54 and is the major extrarenal source of prorenin and Ang II taken-up by the vasculature in young women.55 Although the RAS has been shown to be active in ovaries of fertile women,56,57 the activity of the RAS in the ovary of postmenopausal women has not been fully elucidated. However, ovarian angiotensin-converting enzyme activity, but not plasma angiotensin-converting enzyme, increases with age in postmenopausal women.54 In PMR, ovariectomy at age 16 months almost normalizes blood pressure (Yanes and Reckelhoff, unpublished data, 2004). Therefore, in old female SHR, the ovary very likely contributes some substance that increases their blood pressure, and studies are ongoing to determine the identity of this substance.


*    Does Obesity Play a Role in Postmenopausal Hypertension?
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Many, but not all, women gain weight after menopause, and weight gain is associated with increases in blood pressure and increased incidence of type II diabetes.58 Obesity is also accompanied by an increase in sympathetic activity,59 particularly in the kidney, leading to an increase in renin release that could contribute to hypertension. Therefore, whereas blood pressure increases in most postmenopausal women, obese postmenopausal women have a greater predisposition to hypertension than thinner postmenopausal women. Unfortunately, the PMR gains little weight with age and thus cannot be used to test this hypothesis.


*    Does Activation of the Sympathetic Nervous System Play a Role in Postmenopausal Hypertension?
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Aging in humans is associated with increasing sympathetic activity.60,61 In addition, in obese individuals, whereas total body norepinephrine spillover rates are usually normal, renal norepinephrine spillover is increased.59 Thus, with the combination of aging and obesity in postmenopausal women, there may be greater activation of the sympathetic nervous system than in lean aging women. Therefore, an increase in sympathetic tone may play an important role in mediating postmenopausal hypertension.


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*Summary
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The mechanisms responsible for increases in blood pressure in postmenopausal women are complex and multifaceted. They are not nearly so simple as a reduction in estradiol. Many studies will be necessary to evaluate the importance of the variety of mechanisms described in this review. Although not perfect, it is hoped that the postmenopausal SHR will provide a suitable animal model in which to quantitatively evaluate some of these mechanisms and that the information could be extrapolated to women.


*    Acknowledgments
 
This work was supported by National Institutes of Health HL 66072.


*    Footnotes
 
This article was sent to Friedrich C. Luft, associate editor, for review by expert referees, editorial decision, and final disposition.

Received June 23, 2003; first decision July 23, 2003; accepted February 17, 2004.


*    References
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*References
 
1. Wiinber N, Hoegholm, A, Christensen HR, Bang LE, Mikkelsen KL, Nielsen PE, Svendsen TL, Kampmann JP, Madsen NH, Bentzon MW. 24-h Ambulatory blood pressure in 352 normal Danish subjects, related to age and gender. Am J Hypertens. 1995; 8: 978–986.[CrossRef][Medline] [Order article via Infotrieve]

2. Kannel W. Blood pressure as a cardiovascular risk factor. Prevention and treatment. JAMA. 1996; 275: 1571–1576.[Abstract/Free Full Text]

3. Landahl S, Bengtsson C, Sigurdsson J, Svanborg A, Svardsudd S. Age-related changes in blood pressure. Hypertension. 1986; 8: 1044–1049.[Abstract/Free Full Text]

4. Burl VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, Horan MJ, Labarthe D. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995; 25: 305–313.[Abstract/Free Full Text]

5. August P, Oparil S. Commentary: Hypertension in Women. J Clin Endocrinol Metab. 1999; 84: 1862–1866.[Free Full Text]

6. Thorndike EA, Turner AS. In search of an animal model for postmenopausal diseases. Frontiers in Bioscience. 1998; 3: c17–c26.[Medline] [Order article via Infotrieve]

7. Fang Z, Carlson S, Chen Y, Oparil S, Wyss J. Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2001; 281: R1934–R1939.[Abstract/Free Full Text]

8. Peng N, Clark J, Wei C, Wyss J. Estrogen depletion increases blood pressure and hypothalamic norepinephrine in middle-aged spontaneously hypertensive rats. Hypertension. 2003; 41: 1164–1167.[Abstract/Free Full Text]

9. Fortepiani LA, Zhang H, Racusen LC, Roberts II LJ, Reckelhoff JF. Characterization of an animal model of postmenopausal hypertension in SHR. Hypertension. 2003; 41: 640–645.[Abstract/Free Full Text]

10. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension. 1998; 31: 435–439.[Abstract/Free Full Text]

11. Giummelly P, Lartaud-Idjouadiene I, Marque V, Niederhoffer N, Chillon J-M, Capdevila-Atkinson C, Atkinson J. Effects of aging and antihypertensive treatment on aortic internal diameter in spontaneously hypertensive rats. Hypertension. 1999; 34: 207–211.[Abstract/Free Full Text]

12. Hinojosa-Laborde C, Lange DL, Haywood JR. Role of female sex hormones in the development and reversal of Dahl hypertension. Hypertension. 2000; 35: 484–489.[Abstract/Free Full Text]

13. Javeshghani D, Touyz R, Sairam M, Virdis A, Neves M, Schiffrin E. Attenuated responses to angiotensin II in follitropin receptor knockout mice, a model of menopause-associated hypertension. Hypertension. 2003; 42: 761–767.[Abstract/Free Full Text]

14. James GD, Sealey JE, Muller F, Alderman M, Madhavan S, Laragh JH. Renin relationship to sex, race and age in mormotensive population. J Hypertens. 1986; 4: S387–S389.[CrossRef]

15. Schunkert H, Danser AHJ, Hense H-W, Derkx FHM, Kurzinger S, Riegger GAJ. Effects of estrogen replacement therapy on the renin-angiotensin system in post-menopausal women. Circulation. 1997; 95: 39–45.[Abstract/Free Full Text]

16. Dubey RK, Oparil S, Imthurn B, Jackson EK. Sex hormones and hypertension. Cardiovasc Res. 2002; 53: 688–708.[Abstract/Free Full Text]

17. Nickenig G, Baumer AT, Grohe C, Kahlert S, Strehlow K, Rosenkranz S, Stablein A, Beckers F, Smits JFM, Daemen MJAP, Vetter H, Bohm M. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circulation. 1998; 97: 2197–2201.[Abstract/Free Full Text]

18. Pelzer T, Jager Td, Muck J, Stimpel M, Neyses L. Oestrogen action on the myocardium in vivo: specific and permissive for angiotensin-converting enzyme inhibition. J Hypertens. 2002; 20: 1001–1006.[CrossRef][Medline] [Order article via Infotrieve]

19. Affinito P, Palomba S, Bonifacio M, Fontna D, Izzo R, Trimarco B, Nappi C. Effects of hormone replacement therapy in postmenopausal hypertensive women. Maturitas. 2001; 40: 75–83.[CrossRef][Medline] [Order article via Infotrieve]

20. Cacciatore B, Paakkari I, Hasselblatt R, Nieminen MS, Toivonen J, Tikkanen MI, Ylikorkala O. Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hr ambulatory blood pressure in postmenopausal women. Am J Obstet Gynecol. 2001; 184: 904–909.[CrossRef][Medline] [Order article via Infotrieve]

21. Manhem K, Ahlm H, Milsom I, Svensson A. Transdermal oestrogen reduces daytime blood pressure in hypertensive women. J Hum Hypertens. 1998; 12: 323–327.[CrossRef][Medline] [Order article via Infotrieve]

22. Seely EW, Walsh BW, Gerhard MD, Williams GH. Estradiol with or without progesterone and ambulatory blood pressure in postmenopausal women. Hypertension. 1999; 33: 1190–1194.[Abstract/Free Full Text]

23. Prelevic GM, Kwong P, Byrne DJ, Jagroop IA, Ginsburg J, Mikhailidis DP. A cross-sectional study of the effect of hormone replacement therapy on cardiovascular disease risk profile in healthy postmenopausal women. Fertil Steril. 2002; 77: 945–951.[CrossRef][Medline] [Order article via Infotrieve]

24. Manson J, Hsia J, Johnson K, Rossouw J, Assaf A, Lasser N, Trevisan M, Black H, Heckbert S, Detano R, Strickland O, Wong N, Crouse C, Stein E, Investigators. MCftWsHI. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003; 349: 523–534.[Abstract/Free Full Text]

25. Christ H, Seyffart K, Tillmann HC, Wehling M. Hormone replacement in postmenopausal women: impact of progestogens on autonomic tone and blood pressure regulation. Menopause. 2002; 9: 127–136.[CrossRef][Medline] [Order article via Infotrieve]

26. Fisman EZ, Tenenbaum A, Shapiro I, Motro M, Pines A. Lack of effects of transdermal estradiol on diastolic function: a randomized placebo-controlled double-blind short-term trial. Climacteric. 1999; 2: 174–180.[Medline] [Order article via Infotrieve]

27. Krug E, Berga SL. Postmenopausal hyperthecosis: functional dysregulation of androgenesis in climacteric ovary. Obstet Gynecol. 2002; 99: 893–897.[CrossRef][Medline] [Order article via Infotrieve]

28. Ala-Fossi SL, Maenpaa J, Aine R, Punnonen R. Ovarian testosterone secretion during perimenopause. Maturitas. 1998; 29: 239–245.[CrossRef][Medline] [Order article via Infotrieve]

29. Jiroutek MR, Chen MH, Johnston CC, Longcope C. Changes in reproductive hormones and sex hormone-binding globulin in a group of postmenopausal women measured over 10 years. Menopause. 1998; 5: 90–94.[Medline] [Order article via Infotrieve]

30. Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Muhlen D. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study. J Endocrinol Metab. 2000; 85: 645–651.[Abstract/Free Full Text]

31. Talbott E, Guzick D, Clerici A, Berga S, Detre K, Weimer K, Kuller L. Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler Thromb Vasc Biol. 1995; 15: 821–826.[Abstract/Free Full Text]

32. Mattson LAC, Hamberger L, Samsioe G, Silverstolpe G. Lipid metabolism in women with polycystic ovary syndrome: possible implications for an increased risk of coronary heart disease. Fertil Steril. 1984; 42: 579–584.[Medline] [Order article via Infotrieve]

33. Soranno D, Prasad V, Oberfield DR, Greco A, Sivaraman N, Drucker W. Hypertension and virilization caused by a unique deoxycorticosterone and androgen-secreting adrenal adenoma. J Pediatr Endocrinol Metab. 1999; 12: 215–220.[Medline] [Order article via Infotrieve]

34. Chen Y-F, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992; 19: 456–463.[Abstract/Free Full Text]

35. Ellison KE, Ingelfinger JR, Pivor M, Dzau VJ. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J Clin Invest. 1989; 83: 1941–1945.[Medline] [Order article via Infotrieve]

36. Kesteren PJV, Kooistra T, Lansink M, Kamp GJV, Asscheman H, Gooren LJ, Emeis JJ, Vischer UM, Stehouwer CD. The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning. Thromb Haemost. 1998; 79: 1029–1033.[Medline] [Order article via Infotrieve]

37. Helmersson J, Mattsson P, Basu S. Prostaglandin F(2alpha) metabolite and F2-isoprostane excretion in migraine. Clin Sci (Lond). 2002; 102: 39–43.[Medline] [Order article via Infotrieve]

38. Signorelli SS, Neri S, Sciacchitano S, Pino LD, Costa MP, Pennisi G, Ierna D, Caschetto S. Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness. Maturitas. 2001; 39: 39–42.[CrossRef][Medline] [Order article via Infotrieve]

39. Wilkins FC, Alberola A, Mizelle HL, Opgenorth TJ, Granger JP. Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin. Am J Physiol. 1995; 268: 375–381.

40. Mortenson LH, Pawloski CM, Kanagy NL, Fink GD. Chronic hypertension produced by infusion of endothelin in rats. Hypertension. 1990; 15: 729–733.[Abstract/Free Full Text]

41. Duerrschmidt N, Wippich N, Goettsch W, Broemme HJ, Morawietz H. Endothelin-1 induces NAD(P)H oxidase in human endothelial cells. Biochem Biophys Res Comm. 2000; 269: 713–717.[CrossRef][Medline] [Order article via Infotrieve]

42. Komatsumoto S, Nara M. Changes in the level of endothelin-1 in aging. Nippon Ronen Igakkai Zasshi. 1995; 32: 664–669.[Medline] [Order article via Infotrieve]

43. Schiffrin EL, Turgeon A, Deng LY. Effect of chronic ETA-selective endothelin receptor antagonism on blood pressure in experimental and genetic hypertension in rats. Br J Pharmacol. 1997; 121: 935–940.[CrossRef][Medline] [Order article via Infotrieve]

44. Seo B, Luscher TF. ETA and ETB receptors mediate contraction to endothelin-1 in renal artery of aging SHR. Effects of FR139317 and bosentan. Hypertension. 1995; 25: 501–506.[Abstract/Free Full Text]

45. Earley S, Resta T. Estradiol attenuates hypoxia-induced pulmonary endothelin-1 gene expression. Am J Physiol Lung Cell Mol Physiol. 2002; 283: L86–L93.[Abstract/Free Full Text]

46. Saitta A, Altavilla D, Cucinotta D, Morabito N, Frisina N, Corrado F, D’Anna R, Lasco A, Squadrito G, Gaudio A, Cancellieri F, Arcoraci V, Squadrito S. Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma NO concentrations, endothelin-1 levels and endothelium-dependent vasodilation in postmenopausal women. Arterioscler Thromb Vasc Biol. 2001; 21: 1512–1519.[Abstract/Free Full Text]

47. Alexander BT, Cockrell KL, Rinewalt AN, Herrington JN, Granger JP. Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension. Am J Physiol. 2001; 280: R1388–R1392.

48. Ballew JR, Fink GD. Role of ET(A) receptors in experimental Ang II-induced hypertension in rats. Am J Physiol Regul Integr Comp Physiol. 2001; 281: R150–R154.[Abstract/Free Full Text]

49. Sasser JM, Pollock JS, Pollock DM. Renal endothelin in chronic angiotensin II hypertension. Am J Physiol. 2002; 283: R243–R248.

50. Kahler J, Ewert A, Weckmuller J, Stobbe S, Mittmann C, Koster R, Paul M, Meinertz T, Munzel T. Oxidative stress increases endothelin-1 synthesis in human coronary artery smooth muscle cells. J Cardiovasc Cardio. 2001; 38: 49–57.

51. Hall JE, Brands MJ, Henegar JR. Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney. J Am Soc Nephrol. 1999; 10: S258–S265.[CrossRef][Medline] [Order article via Infotrieve]

52. Reckelhoff JF, Zhang H, Srivastava K, Roberts LJ II, Morrow JD, Romero JC. Subpressor doses of angiotensin II increases plasma F2-isoprostanes in rats. Hypertension. 2000; 35: 476–479.[Abstract/Free Full Text]

53. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest. 1996; 97: 1916–1923.[Medline] [Order article via Infotrieve]

54. DeNuccio I, Salvati G, Genovesi G, Paolini P, Marcellini L, Schiavello V, Re M. Physiopathology of the renin-angiotensin system in the ovary. Minerva Endocrinol. 1999; 24: 77–81.[Medline] [Order article via Infotrieve]

55. Anttila L, Penttila A, Matinlauri I, Koskinen P, Irjala K. Serum total renin levels after ovarian electrocautery in women with polycystic ovary syndrome. Gynecol Endocrinol. 1998; 12: 327–331.[Medline] [Order article via Infotrieve]

56. Ishkovitz J, Rubattu S, Rosenwaks Z, Liu H, Sealey J. Relationship of follicular fluid prorenin to oocyte maturation, steroid levels and outcome with in vitro fertilization. J Clin Endocrinol Metab. 1991; 72: 165–171.[Abstract/Free Full Text]

57. Hassan E, Creatsas G, Mastorakos G, Michalas S. Clinical implications of the ovarian-endometrial renin-angiotensin-aldosterone system. Ann NY Acad Sci. 2000; 900: 107–117.[Medline] [Order article via Infotrieve]

58. Rapelli A. Hypertension and obesity in menopause. J Hypertens. 2002; 20: S26–S28.

59. Esler M, Rumantir M, Wiesner G, Kaye D, Hastings J, Lambert G. Sympathetic nervous system and insulin resistance. From obesity to diabetes. Am J Hypertens. 2001; 14: 304S–309S.[CrossRef][Medline] [Order article via Infotrieve]

60. Seals D, Esler M. Human ageing and the sympathoadrenal system. J Physiol. 2000; 528.3: 407–417.

61. Ng A, Callister R, Johnson D, Seals D. Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension. 1993; 21: 498–503.[Abstract/Free Full Text]




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