-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...

Abstract-Pregnancy impairs baroreflex gain, but the mechanism is incompletely understood. To test the hypothesis that reductions in brain insulin contribute, we determined whether pregnant rats exhibit lower cerebrospinal fluid (CSF) insulin concentrations and whether intracerebroventricular infusion of insulin normalizes gain of baroreflex control of heart rate in conscious pregnant rats. CSF insulin was lower in pregnant (68Ϯ21 pg/mL) compared to virgin (169Ϯ25 pg/mL) rats (PϽ0.05

Recent studies in rabbits suggest that insulin resistance and reduced brain insulin contribute to impaired baroreflex control of heart rate (HR) during pregnancy; however, the mechanisms are unknown. The rat model is ideal to investigate these mechanisms because much is known about rat brain baroreflex neurocircuitry and insulin receptor locations. However, it is unclear in rats whether pregnancy impairs the HR baroreflex or whether insulin resistance is involved. Therefore, this study tested the hypothesis that in rats pregnancy decreases HR baroreflex sensitivity (BRS) and that this decrease is related to concurrent decreases in insulin sensitivity (IS). BRS was quantified before, during, and after pregnancy using complementary methods: 1) spontaneous BRS (sBRS) derived from sequence method analysis of telemetric, continuous arterial pressure recordings; and 2) maximal BRS of complete sigmoidal baroreflex relationships. IS was measured (hyperinsulinemic euglycemic clamp) to determine whether BRS and IS change in parallel. sBRS was reduced at midgestation [pregnancy day 10 (P10)], returned to nonpregnant (NP) levels on P18, and fell again at late gestation (P20) (sBRS in ms/mmHg: NP, 1.66 + or - 0.04; P10, 1.17 + or - 0.11; P18, 1.55 + or - 0.12; P20, 1.31 + or - 0.05; n = 5; P < 0.05). Similar triphasic patterns were observed for both maximal BRS [in beats x min(-1) x mmHg(-1): NP, 4.45 + or - 0.52 (n = 10); P11-12, 2.76 + or - 0.11 (n = 7); P17-18, 3.79 + or - 0.14 (n = 5); P19-20, 2.32 + or - 0.40 (n = 8); P < 0.0001] and previous and current measurements of IS (in mg glucose x kg(-1) x min(-1): NP, 32 + or - 2; P19-20, 15 + or - 1; P < 0.0005). Furthermore, during pregnancy, the standard deviation (SD) of MAP increased, and the SD of HR decreased, indirectly suggesting baroreflex impairment. sBRS increased transiently during parturition, and sBRS, maximal BRS, and IS normalized 3-4 days postpartum. In conclusion, pregnancy decreases HR BRS in rats. The parallel temporal changes in BRS and IS suggest a mechanistic link.

Baroreflex sensitivity (BRS) fluctuates during the menstrual cycle; it reaches its peak during the luteal phase, when gonadal steroids are elevated. However, whether BRS varies during the estrus cycle of the rat is unclear. To test this hypothesis, female rats (n=5) were instrumented for continuous telemetric (24 hr/day; 1000 Hz) measurement of blood pressure (BP) and were housed with a daily light:dark cycle of 12 hr:12 hr. After recovery (10 days), the estrus cycle was established by daily cytologic evaluation of vaginal smears for at least 2 cycles (~10 days). During the following 5–10 days, cardiovagal BRS (in ms/mmHg) was estimated using the sequence method, which selects spontaneous relationships between ramps in systolic BP and associated changes in pulse interval. On each day of the estrus cycle, BRS was increased during lights on (L‐on), compared to lights off (L‐off) (P<0.05). In addition, during L‐on, BRS was elevated on proestrus compared to estrus (1.77±0.11 vs. 1.59±0.08, P<0.05). During L‐off, BRS was increased during protestrus compared to both estrus and metestrus (1.54±0.06 vs. 1.39±0.15 and 1.29±0.04; P<0.05). To test if increases in gonadal hormones underlie the elevated gain on proestrus, rats (n=3) were studied for 4 consecutive days 1–2 weeks following ovariectomy (OVX). In OVX rats, no daily variations in BRS were observed (P>0.50). BRS on each of the 4 days during L‐on was: 1.37±0.20, 1.31±0.18, 1.37±0.20, 1.39±0.07; during L‐off: 1.23±0.06, 1.24±0.05, 1.24±0.01, 1.33±0.06. In summary, cardiovagal BRS fluctuates during the estrus cycle in rats and reaches its peak during proestrus. Because OVX eliminates this daily BRS variation, we conclude that changes in ovarian gonadal steroids mediate this BRS fluctuation. Supported by HL70962, AHA and Collins Fdn.

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