CNS Effects of Ovarian Hormones and Metabolites on Neural Control of Circulation

Heesch, Cheryl M.; Foley, C. Michael

doi:10.1111/j.1749-6632.2001.tb03690.x

Cited by 19 publications

(26 citation statements)

References 44 publications

(97 reference statements)

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“…At least two mechanisms contribute to this. First, increased levels of the neurosteroid metabolite of progesterone, 3␣-hydroxy-dihydroprogesterone (3␣-OH-DHP), decrease the maximal level of sympathetic activity produced during hypotension by increasing GABAergic suppression of premotor neurons in the rostral ventrolateral medulla (3,14). The present results demonstrating reduced GABA influences in PVN suggest that the effect of 3␣-OH-DHP to enhance GABA actions in the PVN is minimal.…”

Section: Discussionmentioning

confidence: 55%

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

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Cassaglia

Brooks

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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It is well established that GABAergic inputs to the paraventricular nucleus of the hypothalamus (PVN) tonically suppress heart rate and the activity of several sympathetic nerves. However, whether GABA similarly inhibits PVN control of baroreflex function has not been previously investigated. To test this hypothesis, it was determined whether microinjection of the GABA A antagonist, bicuculline, into the PVN enhances the baroreflex in anesthetized female virgin rats. In addition, because GABAergic inhibition of PVN preautonomic neurons is decreased during pregnancy, it was also determined whether the effects of PVN bicuculline administration on baroreflex function were less in pregnant animals. In virgin rats, PVN microinjection of bicuculline increased (P Ͻ 0.05) baroreflex gain and maximum levels of heart rate (gain, from 1.6 Ϯ 0.6 to 3.8 Ϯ 1.3 bpm/mmHg; maximum, from 406 Ϯ 18 to 475 Ϯ 14 bpm) and of lumbar sympathetic nerve activity (gain from 2.6 Ϯ 0.7 to 4.8 Ϯ 1.6%/ mmHg; maximum, 149 Ϯ 32 to 273 Ϯ 48%), indicating that PVN GABA normally suppresses baroreflex function. Pregnancy decreased heart rate baroreflex gain (pregnant, 0.9 Ϯ 0.3 bpm/mmHg; virgin, 1.9 Ϯ 0.2 bpm/mmHg; P Ͻ 0.05). Following PVN bicuculline administration in pregnant rats, smaller (P Ͻ 0.01) increments in baroreflex gain (pregnant, 0.6 Ϯ 0.1 bpm/mmHg; virgin, 2.4 Ϯ 0.9 bpm/mmHg) and maximum (pregnant, 33 Ϯ 7 bpm; virgin, 75 Ϯ 12 bpm; P Ͻ 0.05) were produced. Collectively, these data suggest that the PVN normally inhibits the baroreflex via tonic GABAergic inputs and that this inhibition is less during pregnancy. heart rate; baroreceptor reflex; lumbar sympathetic nervous system; ␥-aminobutyric acid THE PARAVENTRICULAR NUCLEUS (PVN) of the hypothalamus integrates multiple forebrain and brain stem inputs to regulate the autonomic nervous system via outputs that ultimately converge with focal brain stem nuclei, such as the rostral ventrolateral medulla, as well as preganglionic sympathetic neurons in the spinal cord (7,27,29,32). While the contribution of the PVN and its connections to basal sympathetic tone at rest in normal animals is minimal, it appears to drive increased sympathetic activity in such pathophysiological states as hypertension, heart failure, and water deprivation (7,27). Moreover, the PVN mediates, in part, autonomic responses to diverse homeostatic challenges, such as changes in food intake, blood volume, stress, and body temperature (29). However, whether and how the PVN can also influence the regulation of the baroreceptor reflex is currently unclear.Of the PVN neurotransmitters and neuromodulators that effect these many functions, the tonically active inhibitory GABAergic inputs to preautonomic neurons are dominant (10, 28). Indeed, local pharmacological blockade of PVN GABA A receptors elicits profound increases in arterial pressure, heart rate (HR), and sympathetic activity and excites neurons that project to the brain stem or spinal cord (15,18,20,22). Therefore, one aim of the present study was to test the hypothes...

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Section: Discussionmentioning

confidence: 55%

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

Page

Cassaglia

Brooks

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In support of this concept, acute systemic administration of the neurosteroid metabolite of progesterone, 3␣-OH-DHP, to nonpregnant rats mimics the effects of pregnancy to suppress arterial baroreflex sympathoexcitation (89,90,124) while having no effect on afferent baroreceptor discharge (115). In all cases, the inactive isomer, 3␤-OH-DHP, was without effect.…”

Section: Neurosteroid Metabolite Of Progesterone: a Contributor To Atmentioning

confidence: 92%

“…Experiments have assessed the site(s) within the baroreflex arc that are functionally depressed. Initial studies documented depressed baroreflex control of multiple efferents, including heart rate (5,21,24,123,175,193), renal and muscle sympathetic nerve activity (79,89,148,149), and hormones such as vasopressin and ACTH/glucocorticoids (26,104). Multiple approaches have been used to assess the effect of pregnancy on reflex control of the autonomic nervous system (for reviews, see Refs.…”

mentioning

confidence: 99%

“…69,163), including infusion of vasoactive drugs to generate complete sigmoidal baroreflex relationships between arterial pressure and heart rate or sympathetic nerve activity. Three aspects of these curves are particularly attenuated: the midpoint of the baroreflex function curve relative to MAP or the "set point," the maximal level of heart rate or sympathetic activity achieved when arterial pressure is lowered, and the maximal gain or sensitivity of the most linear segment of the curve (24,47,89,123,149) (Fig. 1).…”

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confidence: 99%

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Pregnancy and the endocrine regulation of the baroreceptor reflex

Brooks

Dampney

Heesch

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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-The purpose of this review is to delineate the general features of endocrine regulation of the baroreceptor reflex, as well as specific contributions during pregnancy. In contrast to the programmed changes in baroreflex function that occur in situations initiated by central command (e.g., exercise or stress), the complex endocrine milieu often associated with physiological and pathophysiological states can influence the central baroreflex neuronal circuitry via multiple sites and mechanisms, thereby producing varied changes in baroreflex function. During pregnancy, baroreflex gain is markedly attenuated, and at least two hormonal mechanisms contribute, each at different brain sites: increased levels of the neurosteroid 3␣-hydroxydihydroprogesterone (3␣-OH-DHP), acting in the rostral ventrolateral medulla (RVLM), and reduced actions of insulin in the forebrain. 3␣-OH-DHP appears to potentiate baroreflex-independent GABAergic inhibition of premotor neurons in the RVLM, which decreases the range of sympathetic nerve activity that can be elicited by changes in arterial pressure. In contrast, reductions in the levels or actions of insulin in the brain blunt baroreflex efferent responses to increments or decrements in arterial pressure. Although plasma levels of angiotensin II are increased in pregnancy, this is not responsible for the reduction in baroreflex gain, although it may contribute to the increased level of sympathetic nerve activity in this condition. How these different hormonal effects are integrated within the brain, as well as possible interactions with additional potential neuromodulators that influence baroreflex function during pregnancy and other physiological and pathophysiological states, remains to be clearly delineated.3␣-hydroxy-dihydroprogesterone; angiotensin II; insulin; paraventricular nucleus of the hypothalamus NORMAL PREGNANCY is characterized by profound changes in fluid and electrolyte balance and blood pressure regulation. Blood volume and cardiac output increase by 30 -50%, but arterial pressure falls due to even greater decreases in systemic vascular resistance (120,138,189). These hemodynamic alterations are evident early in pregnancy, precede the increases in uterine blood flow, and are sustained until parturition (127,138,189). Considerable data implicate increases in relaxin and nitric oxide (NO) in the systemic vasodilation induced by pregnancy (20,127,128,177,196). In addition, peripheral vascular sensitivity to circulating vasoconstrictors including vasopressin, angiotensin II (ANG II), and norepinephrine (NE) is decreased (50,71,154).Unlike the hemodynamic changes, which likely subserve adequate fetal development, an adverse consequence of normal pregnancy is a marked impairment of the arterial baroreceptor reflex. This change was first noted by Humphreys and Joels (97,98) in an extensive series of studies in anesthetized pregnant rabbits, in which reductions in carotid sinus pressure failed to elicit normal increases in arterial pressure and peripheral vascular resistanc...

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“…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.…”

mentioning

confidence: 93%

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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CNS Effects of Ovarian Hormones and Metabolites on Neural Control of Circulation

Cited by 19 publications

References 44 publications

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

Pregnancy and the endocrine regulation of the baroreceptor reflex

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

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