Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women

Cagnacci, Angelo; Rovati, Lucio C.; Zanni, Anna Lisa; Malmusi, Stefania; Facchinetti, Fabio; Volpe, Annibale

doi:10.1152/ajpheart.1999.276.4.h1355

Cited by 31 publications

(28 citation statements)

References 39 publications

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“…increase nocturnal dipping in postmenopausal women (9,10,29). Collectively, the current and previous studies suggest that gonadal steroids enhance the diurnal variation in cardiovascular regulation.…”

Section: Discussionsupporting

confidence: 64%

Baroreflex sensitivity varies during the rat estrous cycle: role of gonadal steroids

Goldman¹,

Azar²,

Mulvaney³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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-Baroreflex sensitivity (BRS) increases in women during the luteal phase of the menstrual cycle, when gonadal hormones are elevated, but whether a similar cycle-dependent variation in BRS occurs in rats is unknown. In addition, whether cyclic BRS changes depend on gonadal steroids has not been previously investigated. To test these hypotheses, BRS was determined in cycling female rats using two approaches: 1) baroreflex control of renal sympathetic nerve activity (RSNA) in anesthetized rats; 2) cardiovagal spontaneous BRS (sBRS) in conscious rats instrumented for continuous telemetric measurements of mean arterial pressure (MAP) and heart rate (HR). MAP, HR, and sBRS were also measured in rats 2-3 and 5-6 wk following ovariectomy (OVX), to eliminate gonadal steroids. In anesthetized rats, RSNA BRS gain was increased (P Ͻ 0.01) during proestrus (Ϫ4.8Ϯ0.5% control/mmHg) compared with diestrus/estrus (Ϫ2.8 Ϯ 0.3% control/mmHg). Similarly, a proestrous peak in sBRS was observed in conscious rats (1.66 Ϯ 0.07 ms/mmHg, proestrus; 1.48 Ϯ 0.06 ms/mmHg, diestrus/ estrus; P Ͻ 0.001). OVX eliminated estrous cycle-induced variation in sBRS. In addition, OVX reduced (P Ͻ 0.05) diurnal variations in MAP (5.9 Ϯ 0.3 vs. 3.9 Ϯ 0.5 mmHg) and HR [54 Ϯ 4 vs. 39 Ϯ 3 beats per minute (bpm)], and abolished diurnal variations in sBRS. Finally, while MAP, HR, and sBRS were decreased 2-3 wk following OVX, ϳ3 wk later, MAP and sBRS increased, and HR decreased further. No changes in MAP, HR, or sBRS were seen with time in sham OVX controls. In summary, RSNA and cardiovagal sBRS vary during the rat estrous cycle, and this variation is abolished by OVX. We conclude that sex steroid hormones are required for both cyclic and diurnal changes in BRS in rats.renal sympathetic nerve activity; ovariectomy; diurnal; telemetry CONSIDERABLE EVIDENCE INDICATES that gonadal steroids can influence mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity (BRS). First, sex differences have been documented (1,2,5,16,20,27). Second, MAP and HR vary during the estrous cycle of the rat (53), and, in humans, sympathetic BRS increases during the midluteal phase, when gonadal steroid hormone concentrations are higher, compared with the early follicular phase of the menstrual cycle (32). Nevertheless, whether BRS changes during the rat estrous cycle has not been studied. Moreover, whether changes in gonadal steroids underlie the reproductive cycle variability in MAP, HR, and BRS is unclear. Ovariectomy (OVX) and administration of estrogen and/or progesterone have been shown to alter MAP and HR in women and experimental animals; however, results have been conflicting (12,19,31,36,42,53,58). Furthermore, estrogen increases BRS (25,34,40,47); in contrast, a neurosteroid metabolite of progesterone, allopregnanolone, decreases BRS (18). Thus, a clear understanding of the influence of cyclic changes in endogenous gonadal steroids on MAP, HR, and BRS is lacking.Therefore, the primary goal of this study was to determine if BRS varies during the rat estrou...

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Section: Discussionsupporting

confidence: 64%

Baroreflex sensitivity varies during the rat estrous cycle: role of gonadal steroids

Goldman¹,

Azar²,

Mulvaney³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…32 women have revealed a tendency to reduce blood pressure. [33][34][35][36] Cagnacci et al 33 evaluated the effects of 2 months of transdermal oestrogen (50 g/day) on 24-h ambulatory blood pressure in normotensive postmenopausal women. Night-time systolic, diastolic, and mean blood pressures were all significantly reduced in women receiving oestrogen compared with placebo, while there was no difference between groups in daytime blood pressure.…”

Section: Normotensive Womenmentioning

confidence: 99%

Hypertension in women

Rosenthal

Oparil

2000

J Hum Hypertens

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Hypertension in women has received less attention than hypertension in men, and the major controlled trials of antihypertensive therapy have been carried out in populations made up predominantly of and have emphasised outcomes in men. Recently it has been recognised that women develop high blood pressure, particularly systolic hypertension, at an increased rate as they age, and that this age-related blood pressure increase is exaggerated by the menopause. The age-related rise in blood pressure, particularly systolic blood pressure and pulse pressure, contributes substantially to the age-related increase in risk of heart attack, heart failure, and stroke in middle-aged and elderly women. This article reviews

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“…In the Postmenopausal Estrogen/Progestin interventions (PEPI) trial, which enrolled 875 healthy normotensive early postmenopausal women, assignment to conjugated equine estrogens (CEE), 0.625 mg/d ± a progestin did not impact systolic or diastolic BP when compared with placebo controls (PEPI Trial Writing Group, 1995). In contrast, when transdermal E 2 was administered at physiologic doses to healthy postmenopausal women in two studies that evaluated ambulatory BP, active treatment significantly lowered nocturnal systolic, diastolic and mean BP by 3-7 mmHg compared with placebo (Cagnacci et al, 1999;Seely et al, 1999). The observational study component of the WHI (WHI-OS) collected data on risk factors for CVD, including BP, from 98,705 women aged 50-79 yr, the largest multiethnic, best characterized cohort of postmenopausal women ever studied (Wassertheil-Smoller et al, 2000).…”

Section: Estrogen Receptorsmentioning

confidence: 92%

“…Further, BP is reduced when endogenous E 2 levels are elevated during pregnancy (Siamopoulos et al, 1996). Data on the BP effects of estrogen replacement therapy (ERT) in menopausal women have been inconsistent, with reports of BP neutral (PEPI Trial Writing Group, 1995), BP lowering (Mercuro et al, 1997;Mercuro et al, 1998;Cagnacci et al, 1999;Seely et al, 1999;Butkevich et al, 2000) and BP elevating effects (Anderson et al, 2004;WassertheilSmoller et al, 2000). In the Postmenopausal Estrogen/Progestin interventions (PEPI) trial, which enrolled 875 healthy normotensive early postmenopausal women, assignment to conjugated equine estrogens (CEE), 0.625 mg/d ± a progestin did not impact systolic or diastolic BP when compared with placebo controls (PEPI Trial Writing Group, 1995).…”

Section: Estrogen Receptorsmentioning

confidence: 99%