17β-Estradiol inhibits angiotensin II activation of area postrema neurons

Pamidimukkala, Jaya; Hay, Meredith

doi:10.1152/ajpheart.00174.2003

Cited by 37 publications

(29 citation statements)

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“…Studies from our laboratory have shown that 17ß-estradiol facilitates area postrema calciumactivated K + currents and inhibits area postrema neuronal activity (34). 17ß-estradiol also inhibits an increase in (Ca 2+ ) i induced by application of ANG II to cultured area postrema neurons (35). This evidence reinforces the importance of a central antihypertensive action of E2.…”

Section: The Role Of Sex Hormones and Their Central Receptors In Angisupporting

confidence: 58%

Sex differences in angiotensin II- induced hypertension

Xue¹,

Johnson²,

Hay³

2007

Braz J Med Biol Res

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Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG IIinduced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen α receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

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Section: The Role Of Sex Hormones and Their Central Receptors In Angisupporting

confidence: 58%

Sex differences in angiotensin II- induced hypertension

Xue¹,

Johnson²,

Hay³

2007

Braz J Med Biol Res

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“…First, the estrogen profile closely mirrors the pattern of changes in sBRS during the rat estrous cycle (3, 8); a similar direct correlation between the changes in plasma estrogen and baroreflex control of HR has been observed in women during the menstrual cycle (54). Second, numerous studies have demonstrated that estrogen, via an action in the hindbrain, increases BRS (14,23,34,39,47,48). Therefore, we suggest that during proestrus the late afternoon peak in estrogen mediates the increased BRS in the present study.…”

Section: Discussionmentioning

confidence: 57%

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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“…But, one cannot rule out that the low levels of sex hormones present at this early age could also be involved (45,51). Estradiol pretreatment can affect ANG II-induced changes in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in cultured area postrema neurons isolated at P10 to P16 (36), although the effect observed in this group of cells is a reduction in the ANG II-induced increase in [Ca 2ϩ ] i . To directly test whether differences in AT 1 receptor-ImG labeling could also be observed at later time points when sex hormones play a greater role, tissue from young adult (4 mo) and middle-aged (12 mo) rats were analyzed.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in angiotensin signaling in bulbospinal neurons in the rat rostral ventrolateral medulla

Wang

Milner²,

Speth³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Wang G, Milner TA, Speth RC, Gore AC, Wu D, Iadecola C, Pierce JP. Sex differences in angiotensin signaling in bulbospinal neurons in the rat rostral ventrolateral medulla. Am J Physiol Regul Integr Comp Physiol 295: R1149 -R1157, 2008. First published August 6, 2008 doi:10.1152/ajpregu.90485.2008.-Sex differences may play a significant role in determining the risk of hypertension. Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are involved in the tonic regulation of arterial pressure and participate in the central mechanisms of hypertension. Angiotensin II (ANG II) acting on angiotensin type 1 (AT 1) receptors in RVLM neurons is implicated in the development of hypertension by activating NADPH oxidase and producing reactive oxygen species (ROS). Therefore, we analyzed RVLM bulbospinal neurons to determine whether there are sex differences in: 1) immunolabeling for AT 1 receptors and the key NADPH oxidase subunit p47 using dual-label immunoelectron microscopy, and 2) the effects of ANG II on ROS production and Ca 2ϩ currents using, respectively, hydroethidine fluoromicrography and patch-clamping. In tyrosine hydroxylase-positive RVLM neurons, female rats displayed significantly more AT 1 receptor immunoreactivity and less p47 immunoreactivity than male rats (P Ͻ 0.05). Although ANG II (100 nM) induced comparable ROS production in dissociated RVLM bulbospinal neurons of female and male rats (P Ͼ 0.05), an effect mediated by AT 1 receptors and NADPH oxidase, it triggered significantly larger dihydropyridine-sensitive longlasting (L-type) Ca 2ϩ currents in female RVLM neurons (P Ͻ 0.05). These observations suggest that an increase in AT 1 receptors in female RVLM neurons is counterbalanced by a reduction in p47 levels, such that ANG II-induced ROS production does not differ between females and males. Since the Ca 2ϩ current activator Bay K 8644 induced larger Ca 2ϩ currents in females than in male RVLM neurons, increased ANG IIinduced L-type Ca 2ϩ currents in females may result from sex differences in calcium channel densities or dynamics. C1 neurons; reactive oxygen species; NADPH oxidase; calcium channel; estrogen THERE IS INCREASING EVIDENCE that sex differences contribute to the risk of cardiovascular disease, including hypertension (14, 44). Under the age of 45 yr, fewer women than men die from cardiovascular disease (1), a pattern which is reversed after menopause (52). Similar sex-associated differences exist in animal hypertension models: females develop hypertension later, and less severely, than males (11,35,62). Studies in humans and animal models indicate that central nervous system pathways play a critical role in the development and maintenance of hypertension (27). Specifically, increases in sympathetic nerve activity and changes in arterial baroreflex function are strongly implicated in the pathogenesis of the disorder. The rostral ventrolateral medulla (RVLM) contains tonically active presympathetic bulbospinal neurons, most of which express tyrosine hydroxylase (TH) [the C1 cell...

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17β-Estradiol inhibits angiotensin II activation of area postrema neurons

Cited by 37 publications

References 50 publications

Sex differences in angiotensin II- induced hypertension

Sex differences in angiotensin II- induced hypertension

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

Sex differences in angiotensin signaling in bulbospinal neurons in the rat rostral ventrolateral medulla

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