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

Abstract

-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...

Lack of effect of ovarian cycle and oral contraceptives on baroreceptor and nonbaroreceptor control of sympathetic nerve activity in healthy women

“…Despite animal work supporting a hormonal effect on baroreceptor sensitivity (13,17,29,(32)(33)(34), our finding of no change in baroreflex control of SNA with hormonal phase in non-OCP uses is consistent with prior reports in humans (4,12). In these earlier reports, the sympathetic baroreflex sensitivity is assessed by the nonpharmacological approach in which Fig.…”

“…Although estrogen is thought to exert a sympathoinhibitory effect (13,17,24,25,29,38), whereas progesterones may increase resting SNA in humans (6,10), the net effect may depend on the relative level, source (endogenous or exogenous), and bioactivity of each hormone. OCPs contain pharmacological doses of estrogen and progesterone, providing severalfold greater hormonal levels and activity in the plasma and central nervous system compared with endogenous hormones and are metabolized into compounds that are also bioactive.…”

Estradiol potentiates hypothalamic vasopressin and oxytocin neuron activation and hormonal secretion induced by hypovolemic shock

“…The sex steroid hormones are required for changes in baroreflex sensitivity, as shown by the changes that occur in the cardiovagal baroreflex sensitivity and renal sympathetic nerve activity during the estrous cycle of female rats that are abolished by OVX (25). Additionally, several studies have demonstrated the modulation of hypotensive responses by estrogen, although the data are controversial.…”

Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats

“…Furthermore, in conscious ovary-intact female rats the arterial baroreflex control of renal SNA varies across the estrous cycle, suggesting an effect of differing levels of circulating ovarian hormones (18). However, contradictions exist regarding the effects of sex and ovarian hormones on the arterial baroreflex regulation; for example, although previous work has demonstrated that the arterial baroreflex regulation of renal SNA varies across the estrous cycle (3,18), both previous (24,47) and the present evidence have shown that ovariectomy does not alter arterial baroreflex control of renal SNA. Given the potential importance of the arterial baroreflex in mediating changes in SNA in heart failure, future work investigating the mechanistic role of sex and ovarian hormones in mediating the arterial baroreflex is required.…”

“…Sex differences in arterial baroreflex regulation of SNA do exist, with healthy female rats demonstrating a reduced ability of the arterial baroreflex to increase SNA in animals (47,15), a finding confirmed in humans using muscle SNA recordings (52). Furthermore, varying levels of ovarian hormones in females during the reproductive cycle or following menopause can significantly alter arterial baroreflex regulation of SNA (16,18,37,52). It is possible that sex and sex hormone status may contribute to inconsistent findings regarding the arterial baroreflex regulation in heart failure.…”