Citations

The sensitivity of the baroreflex control of muscle sympathetic nerve activity (MSNA) represents the responsiveness of MSNA to changes in blood pressure, whereas the baroreflex threshold diagram evaluates the likelihood of a burst occurrence over a range of resting blood pressure values. We hypothesized that the slope of the threshold diagram would show a significant positive correlation with sympathetic baroreflex sensitivity (BRS). We compared BRS calculated by the Modified Oxford technique (ModOx) with the slope and midpoint (T50) values from threshold analysis (threshold) in 10 participants (9M, age 26 yrs ± 3[mean ± SEM]). MSNA (peroneal microneurography) and blood pressure (brachial catheter) were measured at rest and during vasoactive drug boluses (ModOx). A threshold diagram was created for each subject during rest by associating DBP to the % occurrence of a burst over a 4 min period prior to the ModOx drugs. The midpoint (T50) of this diagram was defined as the DBP at which 50% of the diastoles were associated with a burst. ModOx‐derived BRS positively correlated with the slope of the threshold diagram (r = 0.64, P<0.05), but not with the T50 (r =0.11, P > 0.2). Our results suggest that the slope of the threshold diagram may be a better index of ModOx‐derived BRS values compared to more commonly used "spontaneous" baroreflex techniques. NIH HL‐083947

Inter‐individual variability in hemodynamic variables appears to be important in human blood pressure regulation. It is not known whether the rat, often used for studies of cardiovascular regulation, exhibits similar inter‐individual variability. In the present study, we evaluated whether inter‐individual variability in cardiac output (CO) and total peripheral resistance (TPR) is similar in humans and in rats, and whether a balance between these variables is similar in the two species. We assessed the relationship between CO and TPR during control conditions in humans (N = 40) and in Sprague‐Dawley rats (N = 16). We further assessed whether the relationship between CO and TPR was altered during acute increases in blood pressure, which were accomplished in humans with acute systemic L‐NMMA (N = 17), and in rats with a DOCA‐salt model (N = 16). Both humans and rats showed marked inter‐individual variability in CO and TPR but low variability in blood pressure. In both species, CO and TPR showed strong inverse correlations during normotension (r 2 = 0.88 (humans) and 0.89 (rats)) and during blood pressure increases (r 2 = 0.91 (humans) and 0.58 (rats)). We conclude that inter‐individual variability CO and TPR, and the balance between these variables, are important aspects of blood pressure regulation in both humans and rats. Supported by NIH HL32352, HL83947, HL64176, UL1‐RR24150 and Swedish Research Council 12170.

Previous data indicate that endothelin‐1 may have a direct excitatory effect on sympathetic nerve activity in animals and hypertensive humans. Whether this is true in normotensive humans is unclear. We investigated the relationship between endogenous endothelin‐1 and muscle sympathetic nerve activity (MSNA) in 15 normotensive young men and 15 women (age; 25 ± 1 vs. 25 ± 2 yrs, BMI; 25 ± 1 vs. 23 ± 1 kg/m2). MSNA was recorded via peroneal microneurography, arterial pressure was estimated from brachial arterial line and serum levels of endothelin‐1 (brachial artery) was measured by a quantitative two‐site chemiluminescent immunoassay. Mean arterial pressure (MAP, 90 ± 2 vs. 93 ± 2 mmHg), MSNA (37 ± 3 vs. 34 ± 4 bursts/100 heart beats) and endothelin‐1 (0.72 ± 0.03 vs. 0.63 pg/mL) were not different between men and women respectively. Interestingly, resting MSNA was positively related to arterial levels of endothelin‐1 in men (r = 0.69, P<0.05) but not in women (r = 0.03). Thus, men with high MSNA had high levels of endothelin‐1. These data suggest that endogenous endothelin‐1 is linked to tonic levels of sympathetic nerve activity in men but not in women. AHA 2170087 (ECJH); HL083947 (NC, MJJ, BGW); NIH RR024150 (CTSA).

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.

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

The purpose of this study was to evaluate the relationship between the cardiac and sympathetic baroreflex sensitivities within healthy, young individuals. The gains in cardiac (as measured by changes in R‐R interval, RRI, and heart rate, HR) and sympathetic (as measured by changes in muscle sympathetic nerve activity, MSNA) baroreflex during rapid changes in arterial blood pressure were compared in 27 normotensive individuals (18 men and 9 women; age 24 yrs ±1.24; body mass index 24 ±0.51 cm/kg 2 , mean ±SEM). Heart rate, arterial blood pressure (brachial artery catheter), and peroneal MSNA were recorded under resting conditions (HR 58 ±1.6 bpm; SBP 124 ±2.7 mmHg; DBP 71 ±1.7 mmHg; MAP 87 ±1.7 mmHg; MSNA BF 17 ±1.6 bursts/min) as well as during rapid changes in arterial blood pressure induced by sequential boluses of nitroprusside and phenylephrine (Modified Oxford technique). Integrated baroreflex sensitivities for MSNA and HR were analyzed using the slopes of the linear portions of the MSNA‐diastolic blood pressure and RRI‐systolic blood pressure relationships, respectively. When individual cardiac baroreflex sensitivity was compared to sympathetic baroreflex sensitivity, no correlation (R 2 =0.0003) was found. These results indicate that although both cardiac and sympathetic efferents function in baroreflex control of the autonomic system, there does not appear to be a direct correlation in their function within healthy normotensive individuals. Research Support: NIH HL083947 and Swedish Medical Council grant 12170

Young men display a positive association between breathing rate and muscle sympathetic nerve activity (MSNA). We compared breathing rate, peroneal MSNA and cardiovascular variables at rest in 17 men (age 27 ± 2 yrs) and 15 women (age 25 ± 1 yrs). Breathing rates and MSNA were similar in men and women but women had significantly lower systolic and mean blood pressures, cardiac output and stroke volume. In men breathing rate correlated positively to MSNA (r = 0.58, p<0.05) but not in women (r = 0.12, p> 0.05).. In men respiratory rate correlated positively to total peripheral resistance (r = 0.65, p<0.05) and inversely to cardiac output (r = − 0.84, p<0.05) and heart rate (r = − 0.60, p<0.05) but there were no such relationships in women (p> 0.05 for all). In another group of subjects, linear regression was performed on respiratory rate and brachial arterial plasma norepinephrine. There was no relationship in men (r=0.0847, n=38) or women (r=0.0367, n=74). Importantly, MSNA does not always predict plasma NE levels at rest. The positive relationship between breathing and MSNA in men, and the inverse coupling of breathing to cardiac output and heart rate suggest that influences of respiration may be important, not only for dynamic, but also for “tonic” cardiovascular function. The lack of relationships among these variables in women shows that there are fundamental differences in basic blood pressure regulation between the sexes.

On a beat‐by‐beat basis, withdrawal of baroreflex inhibition results in a burst of (muscle) sympathetic nerve activity (MSNA) as well as a decrease in the cardiac interval due to vagal withdrawal. The aim of this study was to quantify the cardiac and vascular components of the hemodynamic response following individual bursts of MSNA. We measured MSNA (peroneal microneurography), arterial pressure (AP, directly) and cardiac output (CO, acetylene uptake) in 11 healthy supine subjects. Beat‐by‐beat CO was also derived by arterial pulse wave analysis (Modelflow) and calibrated to the measured CO. Total peripheral resistance (TPR) was calculated as meanAP/CO. For each subject, the mean change in diastolic AP, inter‐beat interval (IBI), CO and TPR were calculated for each of 15 cardiac cycles following a burst of MSNA. We found a transient increase in diastolic AP (1.9±.34 mmHg), CO (.097±.026 l/min) and TPR (.023±.007 mmHg/l/min) and a transient shortening of IBI (−16±4 ms). Maxima occurred 5.8, 2.7, 6.1 and 2.6 s, respectively, after the beat that triggered the burst. There was a linear relation between MSNA (burst incidence) at baseline and time to maximum AP increase (r=.75, p=.008) as well as to time to maximum TPR (r=.69, p=.01). This suggests that subjects with higher resting MSNA have delayed hemodynamic responses following individual bursts. Support: NIH NS32352, NL Heart Found. 2004/T007, Fulbright program