Charkoudian, Nisha

Acute ß‐adrenergic blockade (BB) increases aortic wave reflection in young women, however, it is unknown if this effect extends to post‐menopausal women. Thus, we examined systemic BB on aortic wave reflection in 14 post‐menopausal women (58 ± 2 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity radial pressure waveforms obtained from applanation tonometry before and during systemic BB (0.25mg/kg bolus, with 0.004 mg/kg/min continuous infusion of propranolol). Aortic blood pressure, augmentation index (AIx), AIx adjusted for heart rate (AIx@75), aortic augmented pressure (AP), and wasted left ventricular energy (Ew) were calculated from the aortic pressure waveform. Heart rate (60 ± 2 vs. 51 ± 2 bpm) and mean arterial pressure (95 ± 3 vs. 91 ± 3 mmHg) were reduced with BB (P < 0.05 for both). AIx increased during BB (32 ± 2 vs. 35 ± 2%, P < 0.01), however, AIx@75 was unchanged (25 ± 2 vs. 24 ± 2%, ns). Additionally, AP (20 ± 2 vs. 20 ± 2 mmHg, ns) and Ew (4313 ± 538 vs. 4277 ± 537 dyne*cm2/sec, ns) remained unchanged during BB. When compared to our previously published study in young women, indices of aortic wave reflection were significantly less affected in post‐menopausal women in response to acute systemic BB. Taken together, our data suggest that the negative effects (i.e. increased aortic wave reflection) of non‐selective BB are less pronounced in post‐menopausal women.

Yoga is thought to reduce stress; however, few studies have quantified plasma levels of stress hormones. Yoga includes physical postures, meditation, and pranayama (controlled breathing) therefore it is difficult to determine which dose and combination of these components is most beneficial. We hypothesized that a single 15 min bout of 6 breaths per minute would be sufficient to cause a reduction in stress hormones. Ten young healthy males (age 18–35, n=10) were instrumented with brachial arterial catheter for blood draws and respiration was monitored continuously using a double pneumobelt. Blood draws were taken after 15 min of supine rest with baseline ventilation and again after 15 min of slow paced breathing. Average baseline supine respiratory rate was 12.1 ± 0.5 breaths/min and during slow breathing it was 5.5 ± 0.4 breaths/min (p<0.05). After 15 min of slow breathing in the supine position there was a significant reduction in arterial norepinephrine (173.9 ± 15.5 vs 135.6 ± 42.9, p=0.002), cortisol (8.2 ± 0.7 vs 7.3 ± 0.59, p=0.002), and adrenocorticotrophic hormone (ACTH, 15.5 ± 2.4 vs 13.4 ± 2.2, p=0.009). As well, there was a trend for reduction in arterial epinephrine (82 ±28.2 vs 42.7 ± 9.7, p=0.15). These changes are consistent with a reduction in sympathetic nerve activity and a blunting of cortisol. In summary, acute yogic breathing significantly reduces stress hormones.

In young women, tonic autonomic nervous system activity contributes less to resting blood pressure than that in men. It is unknown whether the autonomic support of blood pressure increases in postmenopausal women, therefore we examined the effect of autonomic blockade on blood pressure and how this relates to baseline muscle sympathetic nerve activity (MSNA) in women. Five young (23±4 yr) and 6 older (57±3 yr) women were examined before and during autonomic blockade using trimethaphan camsylate (TM). MSNA burst frequency and burst incidence were higher in older women (24±2 vs. 14±3 bursts/min; 41±3 vs. 23±5 bursts/100hb, respectively; p<0.05). Older women had a greater drop in mean arterial pressure (MAP; −25±2 vs. −8±3 mmHg; p<0.01) and total peripheral resistance (−0.7±0.1 vs. −0.2±0.1 AU; p<0.01) during autonomic blockade. MSNA bursts were abolished by TM within minutes. Baseline burst frequency and burst incidence were associated with the decrease in MAP during autonomic blockade (r=−0.64, r=−0.63; respectively; p<0.05). In conclusion, autonomic blockade reduces MAP to a greater extent in older women, and this decrease in blood pressure is associated with resting levels of MSNA. Our results suggest that autonomic support of blood pressure is greater in older women compared to young women. Elevated sympathetic nerve activity may explain the increased incidence of hypertension after menopause.

Aortic wave reflection increases with age, and is influenced by numerous factors, including sympathetic nerve activity. The purpose of this study was to examine the effect of autonomic blockade using trimethaphan camsylate on indices of aortic wave reflection in young (23±4 yr) and older postmenopausal (57±3 yr) women and determine if aging alters these interactions. Arterial tonometry was used to non‐invasively measure arterial waveforms from the radial artery before and during trimethaphan infusion. Aortic augmentation index (AI x ), augmented pressure, and left ventricular wasted energy (E w ) were higher in older women compared to young women at baseline (p<0.05). Mean arterial pressure was similar between young (93±5 mmHg) and older women (91±2 mmHg) at baseline. AI x (Δ −12±5%), augmented pressure (Δ −11±4 mmHg), and E w (Δ −2364±1020 dyne·cm 2 ·sec) decreased after autonomic blockade in older women (p<0.05 for all). In addition, the age‐related differences in AI x and aortic wave reflection persisted during autonomic blockade (p<0.05). In conclusion, autonomic blockade reduces augmentation index and aortic wave reflection in older women. Our results suggest that sympathetic activity contributes to the higher aortic wave reflection observed in older women.

Vascular function in older women versus young women may differ based on the β‐adrenergic receptor‐mediated contribution to basal vascular tone. Thus, we tested the hypothesis that forearm blood flow (FBF) responses to the β‐receptor agonist isoproterenol (ISO) are blunted in older, postmenopausal women compared to young, premenopausal women. We used venous occlusion plethysmography to measure FBF in young (26 ± 3 yr; n = 13) and older (61 ± 6 yr; n = 12) women. FBF and mean arterial pressure (MAP) were measured at baseline and during ISO infusion at 1.0, 3.0, 6.0, and 12.0 ng/100 ml tissue/min. The two groups did not differ in body mass index or MAP. Baseline FBF (3.7 ± 1.7 vs. 2.9 ± 1.3 ml/100 ml/min, respectively) and forearm vascular conductance (FVC) (0.04 ± 0.02 vs. 0.03 ± 0.01 AU, respectively) were similar between young and older women. FBF and FVC remained similar between the groups for all ISO doses, including the 12.0 ng/100 ml tissue/min dose of ISO, for which the greatest difference between the groups would be expected; FBF was 10.7 ± 2.3 vs. 9.4 ± 2.1 ml/100 ml/min (young vs. older, respectively) and FVC was 0.11 ± 0.02 vs. 0.10 ± 0.02 AU (young vs. older, respectively). In conclusion, β‐adrenergic receptor‐mediated forearm responses to stimulation are similar between young and older women, suggesting that β‐adrenergic receptor response and contribution to vascular tone are preserved with aging in women. Funded by NIH

Slow‐paced breathing is a simple strategy to reduce psychological stress. We tested the hypothesis that slow paced breathing would decrease muscle sympathetic nerve activity (MSNA). Ten young, healthy males were studied. The subjects were instructed to rest supine and breathe normally (baseline) or at six breaths per minute, each for 20 minutes. MSNA was measured (peroneal microneurography) and analyzed 5 minutes into each stage for a steady state measurement. Statistical analysis was completed using one way RM ANOVA and Tukey’s posthoc analysis (reported mean±SEM). Average respiratory rate was 11.9 ± 1.1 breaths/min during baseline and 5.8 ± 0.7 breaths/min during slow‐paced breathing. There was no significant difference from baseline compared to slow paced breathing in MSNA burst frequency (18±2.0 vs 18±2.40 bursts/min), burst incidence (31.2±4.01 vs. 30.4±3.80 bursts/100 heartbeats) or burst area (12.70±2.18 vs 13.02±1.98%). However, there was a change in the pattern of burst firing with a significant increase in quiescent periods between burst clusters during slow paced breathing compared to baseline (6.50±0.61 vs. 3.59±0.41 seconds), which was accompanied by a significant decrease in the number of bursts/cluster (2.9±0.38 vs. 5.6±0.8 bursts). This has physiological relevance since there was a significant decrease in plasma norepinephrine, increase in blood flow, and a reduction in mean arterial pressure during these same periods. These findings indicate that despite no change in burst incidence, slow paced breathing alters the pattern of MSNA firing, which may contribute to favorable cardiovascular changes. Grant Funding Source : Supported by NIH HL‐083947

The relationship between mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and total peripheral resistance (TPR) is altered in young women versus men and postmenopausal women due to endogenous sex hormone differences. Exogenous sex hormones in the form of oral contraceptive pills (OCPs) may further affect this relationship. We performed a retrospective review of 136 premenopausal women in whom MSNA and arterial pressure were measured, including 78 women with natural menstrual cycles in the early follicular phase (26±1 yr) and 58 women in the placebo phase of OCPs (24±1 yr). TPR and cardiac output (CO) were measured in a subset of women in whom continuous intra‐arterial blood pressure was recorded. Compared to those with natural menstrual cycles, women on OCPs had greater MAP (89±1 vs. 84±1 mmHg, p<0.01) and tended to have lower MSNA (15±1 vs. 18±1 bursts/100 heart beats, p=0.06). MAP and MSNA were positively correlated (r=0.22, p<0.05), TPR and MSNA were positively associated (r=0.41, p<0.05) and CO and MSNA (r=‐0.44, p<0.05) were inversely associated in naturally cycling women (n=26) but not in women on OCPs (r=0.15, r=0.11, r=‐0.01, respectively; p>0.05; n=38). In contrast to naturally cycling women, there appears to be no relationship between MSNA and hemodynamics in women on OCPs, suggesting that these women may regulate their blood pressure differently than women. Grant Funding Source : Supported by NIH

In men, muscle sympathetic nerve activity (MSNA) is positively related to total peripheral resistance (TPR) and inversely related to cardiac output (CO). However, this relationship was not observed in young women. We aimed to investigate whether simultaneous β ‐adrenergic stimulation offsets this balance in young women. We measured MSNA (peroneal microneurography), arterial pressure (brachial line), CO (open‐circuit acetylene) and TPR before and after systemic β ‐blockade with propranolol in 6 young normotensive women (age; 24 ± 2 yrs, body mass index; 23 ± 1 kg/m 2 ). There was no difference in CO (5.7 ± 0.3 L vs. 5.3 ± 0.4 L), mean arterial pressure (MAP; 95 ± 3 mmHg vs. 95 ± 2 mmHg) before and after beta‐blockade. However, there was significant reduction in heart rate (HR; 61 ± 3 beats/min vs. 55 ± 2 beats/min, P <0.05). β ‐blockade caused an increase in TPR (17.4 ± 1.2 mmHg/ml/min vs. 18.5 ± 1.3 mmHg/ml/min; P =0.07) and MSNA (28 ± 3 bursts/100hb vs. 33 ± 3 bursts/100hb, P =0.08). Before β ‐blockade there was no relationship of MSNA to TPR, CO or MAP. Following β ‐blockade, there was a positive relationship between TPR and MSNA (r=0.60). However, there was no relationship of MSNA to cardiac output (r = −0.12). Interestingly, MAP became related to MSNA (r = 0.56). In summary, the β ‐adrenergic receptors appear to play a key role in the sympatho‐hemodynamic balance in young women. AHA 09POST2170087

We examined the relationship between total peripheral resistance (TPR) and central artery pressure and indices of wave reflection in 16 subjects (10F/6M; 26 ± 1 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity radial pressure waveforms obtained from applanation tonometry of the radial artery. Radial blood pressure (BP) was calibrated from brachial artery BP (catheter). Central artery pressures, aortic augmentation index (AI a ), roundtrip travel time of the reflected wave to and from the periphery (Δt p ; inverse of pulse wave velocity), and wasted left ventricular energy (E w ) were calculated from the generated aortic pressure waveform. Cardiac output (CO) was measured using an open‐circuit acetylene uptake technique and used to calculate total peripheral resistance (mean arterial pressure/CO). TPR was positively related to aortic pulse pressure (r = 0.49), augmented pressure of the central artery wave (r = 0.60), pulse pressure amplification (r =0.54), AI a (r = 0.53), and E w (r = 0.66), (P < 0.05 for all). Additionally, TPR was inversely related to Δt p (r = − 0.51, P < 0.05). Our data suggests that increased levels of TPR are related to measures of central artery pressure, wave reflection characteristics and indices of central artery stiffness. Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150

We examined the effects of acute β‐adrenergic blockade on central artery hemodynamics and wave reflection characteristics in young healthy humans. High‐fidelity radial artery waveforms were recorded non‐invasively by applanation tonometry before and after intravenous propranolol (0.25 mg/kg bolus for 5 min followed by a maintenance infusion of 0.004/mg/kg/min for 20–30 min) in fourteen subjects (9 F/5M; 27 ± 2 years). Radial blood pressure (BP) was calibrated from the brachial BP (arterial catheter). Aortic augmentation index (AI a ; a measure of amplitude and timing of arterial pressure wave reflection) and roundtrip travel time of the reflected wave to and from the periphery (Δt p ; inverse of pulse wave velocity) were calculated from the generated aortic pressure waveform and are indices of central arterial stiffness. Systemic β‐blockade reduced heart rate (HR; 60 ± 2 vs. 53 ± 2 bpm, P < 0.001) and increased AI a (9.9 ± 4.3% vs. 4.3 ± 4.4%, P < 0.05), but did not alter Δt p (156 ± 4 msec vs. 152 ± 2 msec, P = 0.34). The AI a normalized to a HR of 75bpm (AI a @75) was not increased following β‐blockade (P = 0.67). Taken together, our data indicate that the increase in AI a following systemic β‐blockade is a result of a slower HR and not due to changes in β‐ mediated vascular tone. Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150