Carter JR, Lawrence JE, Klein JC. Menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. Am J Physiol Endocrinol Metab 297: E85-E91, 2009. First published April 28, 2009 doi:10.1152/ajpendo.00019.2009.-Sympathetic baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) responses during early follicular (EF) and midluteal (ML) phases of the menstrual cycle are controversial. We hypothesize an augmented sympathetic BRS and MSNA response to orthostatic stress during the ML phase of the menstrual cycle. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP) (Ϫ5, Ϫ10, Ϫ15, Ϫ20, Ϫ30, and Ϫ40 mmHg; 3 min/stage) in 13 healthy, eumenorrheic women (age 21 Ϯ 1 yr). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA at rest and during progressive LBNP. Plasma estradiol (42 Ϯ 6 vs. 112 Ϯ 12 pg/ml; P Ͻ 0.01) and progesterone (2 Ϯ 0 vs. 10 Ϯ 2 ng/ml; P Ͻ 0.04) were elevated during the ML phase. Resting MSNA (8 Ϯ 1 vs. 11 Ϯ 1 bursts/min), MAP (79 Ϯ 2 vs. 78 Ϯ 2 mmHg), and HR (58 Ϯ 2 vs. 60 Ϯ 2 beats/min) were not different during EF and ML phases. MSNA and HR increased during progressive LBNP (P Ͻ 0.001), and the increases in MSNA burst frequency (bursts/min) and HR were similar during both phases. In contrast, increases in total MSNA (arbitrary units) during progressive LBNP were augmented during the ML phase (P Ͻ 0.04), but this response does not appear to be linked to differences in sympathetic BRS. Progressive LBNP did not change MAP during either phase. Our results demonstrate an augmentation of the MSNA response to progressive LBNP during the ML phase of the menstrual cycle. These findings suggest that hormonal fluctuations of eumenorrheic women may influence sympathoexcitation during an orthostatic challenge, but not through sympathetic baroreflex-mediated pathways. muscle sympathetic nerve activity; arterial blood pressure; lower body negative pressure; baroreflex; estrogen EVIDENCE SUGGESTS THAT ORTHOSTATIC intolerance is more prevalent in women compared with men (3,5,7,19,(21)(22)(23). The mechanisms responsible for this apparent sex difference are presently unclear, but altered patterns of sympathoexcitation have been suggested. Shoemaker et al. (22) reported a blunted muscle sympathetic nerve activity (MSNA) response to orthostatic stress in women compared with men, suggesting MSNA responses to an orthostatic challenge may contribute to the higher incidence of orthostatic intolerance in women. In contrast, Fu et al. (9) recently reported that sex did not affect MSNA responses to an orthostatic challenge. The influence of sex on MSNA responses to orthostatic stress remains debatable.Shoemaker et al. (22) and Fu et al. (8) did not control for menstrual phase in their female subjects; thus, it is possible that differences between these two studies were due to hormonal fluctuations associated with the menstrua...

Durocher JJ, Klein JC, Carter JR. Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans. Am J Physiol Heart Circ Physiol 300: H1788-H1793, 2011. First published February 25, 2011 doi:10.1152/ajpheart.00942.2010.-Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (Ͼ0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope ϭ Ϫ1.95 Ϯ 0.18 bursts·(100 beats) Ϫ1 ·mmHg Ϫ1 ; r ϭ Ϫ0.86 Ϯ 0.03] or total MSNA [slope ϭ Ϫ438 Ϯ 91 units·(beat) Ϫ1 mmHg Ϫ1

Recent studies report that the menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. The purpose of the present study was to determine whether oral contraceptives (OC) influence sympathetic neural activation during an orthostatic challenge. Based on evidence that sympathetic baroreflex sensitivity (BRS) is increased during the "low hormone" (LH) phase (i.e., placebo pills) in women taking OC, we hypothesized an augmented muscle sympathetic nerve activity (MSNA) response to orthostatic stress during the LH phase. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP; -5, -10, -15, -20, -30, -40 mmHg; 3 min/stage) in 12 healthy women taking OC (age 22 +/- 1 years). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA. Subjects were examined twice: once during LH phase and once approximately 3 wk after LH during the "high hormone" phase (randomized order). Resting MSNA (10 +/- 2 vs. 13 +/- 2 bursts/min), MAP (85 +/- 3 vs. 84 +/- 3 mmHg), and HR (62 +/- 2 vs. 65 +/- 3 beats/min) were not different between phases. MSNA and HR increased during progressive LBNP (P < 0.001), and these increases were similar between phases. Progressive LBNP did not change MAP during either phase. Sympathetic BRS increased during progressive LBNP, but these responses were not different between LH and high hormone phases. In conclusion, our results demonstrate that OCs do not alter cardiovascular and sympathetic neural responses to an orthostatic challenge in young, healthy women.

This study examined the effect of combined heat and mental stress on neurovascular control. We hypothesized that muscle sympathetic nerve activity (MSNA) and forearm vascular responses to mental stress would be augmented during heat stress. Thirteen subjects performed 5 min of mental stress during normothermia (Tcore; 37 ± 0°C) and heat stress (38 ± 0°C). Heart rate, mean arterial pressure (MAP), MSNA, forearm vascular conductance (FVC; venous occlusion plethysmography), and forearm skin vascular conductance (SkVCf; via laser-Doppler) were analyzed. Heat stress increased heart rate, MSNA, SkVCf, and FVC at rest but did not change MAP. Mental stress increased MSNA and MAP during both thermal conditions; however, the increase in MAP during heat stress was blunted, whereas the increase in MSNA was accentuated, compared with normothermia (time × condition; P < 0.05 for both). Mental stress decreased SkVCf during heat stress but not during normothermia (time × condition, P < 0.01). Mental stress elicited similar increases in heart rate and FVC during both conditions. In one subject combined heat and mental stress induced presyncope coupled with atypical blood pressure and cutaneous vascular responses. In conclusion, these findings indicate that mental stress elicits a blunted increase of MAP during heat stress, despite greater increases in total MSNA and cutaneous vasoconstriction. The neurovascular responses to combined heat and mental stress may be clinically relevant to individuals frequently exposed to mentally demanding tasks in hyperthermic environmental conditions (i.e., soldiers, firefighters, and athletes).

The menstrual cycle has been reported to alter mean arterial pressure (MAP), but not muscle sympathetic nerve activity (MSNA), during vestibular activation. Specifically, MAP responses to head-down rotation (HDR) are augmented during the midluteal (ML) phase compared to the early follicular (EF) phase in young, eumenorrheic women. The purpose of the present study was to determine if the menstrual cycle influences vestibular-mediated changes in limb blood flow. MSNA, MAP, heart rate, and limb blood flow responses to HDR were measured in 12 healthy women. Resting MSNA, MAP, heart rate, forearm blood flow and calf blood flow were not altered by the menstrual cycle. HDR elicited similar increases in MSNA during the EF (Δ3 ± 1 bursts/min; P < 0.05) and ML (Δ2 ± 1 bursts/min; P < 0.05) phase, but only increased MAP during the ML phase (Δ4 ± 2 mmHg; P < 0.05). HDR did not change heart rate during either the EF or ML phase. HDR elicited similar increases in calf vascular resistance during the EF (Δ6 ± 2 mmHg/mL/100mL/min; P < 0.05) and ML (Δ7 ± 2 mmHg/mL/100mL/min; P < 0.05) phases of the menstrual cycle. In contrast, HDR increased forearm vascular resistance during the ML phase (Δ4 ± 2 mmHg/mL/100mL/min; P<0.05), but not the EF phase (Δ0 ± 2 mmHg/mL/100mL/min). These findings suggest an increased transduction of sympathetic nerve activity into forearm vascular resistance during the ML phase, and reveal the first recorded divergent vascular response to vestibular excitation in human limbs.