Abstract 019: Effect of CPAP on Blood Pressure and Central Sympathetic Outflow in Diabetic Patients with OSA, Resistant HTN, and CKD

Introduction: Central sympathetic hyperactivity as assessed by muscle sympathetic nerve activity recordings is thought to play a crucial role in the development and maintenance of hypertension (HTN) in patients with obstructive sleep apnea (OSA). Decreases in daytime and nocturnal blood pressure (BP) in response to treatment with continuous positive airway pressure (CPAP) are paralleled by decreases in muscle sympathetic nerve activity (MSNA). Patients with chronic kidney disease (CKD) have high MSNA. Bilateral nephrectomy, but not renal transplantation normalizes MSNA indicating central sympathoexcitatory effects by renal afferents. The objective of this study was to assess to what extent is HTN driven by central sympathetic hyperactivity in patients with diabetic CKD, OSA, and resistant HTN. Thirteen patients (age 62.2±7.4 years) with diabetic CKD, resistant HTN defined as SBP on 24-hr ABPM above 135 mmHg while on 3 or more BP lowering drugs (including diuretic) with OSA, were randomized to therapeutic CPAP or non-therapeutic CPAP for one months. 24-hr ABPM, plasma catecholamines, aldosterone, and renin, and MSNA were assessed before and 1 months after randomization. Our results show (Table) that in contrast to sham CPAP, therapeutic CPAP decreased daytime and nighttime BP. In contrast, neither therapeutic nor sham CPAP caused any changes in MSNA and plasma catecholamines. In conclusion, decreases in BP in response to CPAP in patients with in diabetic CKD, despite maintained high MSNA, indicate other mechanism contributing to HTN in these patients as well as other central sympathoexcitatory pathways activated.

Download Full-text

Role Of Muscle Sympathetic Nerve Activity And Vascular Responsiveness In Mediating Increased Blood Pressure Following Exposure To Cyclic Intermittent Hypoxia

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a6372 ◽

2011 ◽

Author(s):

Bethany P. Kulczewski ◽

Geoffrey S. Gilmartin ◽

Jason W. Hamner ◽

Mekkin E. Lynch ◽

Patrick Troy ◽

...

Keyword(s):

Blood Pressure ◽

Sympathetic Nerve ◽

Intermittent Hypoxia ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Nerve Activity ◽

Vascular Responsiveness

Download Full-text

Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00253.2009 ◽

2010 ◽

Vol 299 (3) ◽

pp. H925-H931 ◽

Cited By ~ 73

Author(s):

G. S. Gilmartin ◽

M. Lynch ◽

R. Tamisier ◽

J. W. Weiss

Keyword(s):

Blood Pressure ◽

Sympathetic Nerve ◽

Intermittent Hypoxia ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Chronic Intermittent Hypoxia ◽

Sympathetic Activation ◽

Nerve Activity ◽

Blood Pressure Elevation ◽

Healthy Humans

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17–24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr ( n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 ± 1.3 vs. 74 ± 1.7 mmHg, P < 0.01), MSNA [9.94 ± 2.0 to 14.63 ± 1.5 bursts/min ( P < 0.05); 16.89 ± 3.2 to 26.97 ± 3.3 bursts/100 heartbeats (hb) ( P = 0.01)], and forearm vascular resistance (FVR) (35.3 ± 5.8 vs. 55.3 ± 6.5 mmHg·ml−1·min·100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

Download Full-text

Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00842.2012 ◽

2013 ◽

Vol 304 (5) ◽

pp. H759-H766 ◽

Cited By ~ 63

Author(s):

Seth T. Fairfax ◽

Jaume Padilla ◽

Lauro C. Vianna ◽

Michael J. Davis ◽

Paul J. Fadel

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Burst Size ◽

Muscle Sympathetic Nerve Activity ◽

Common Femoral Artery ◽

Vascular Conductance ◽

Nerve Activity ◽

Arterial Blood

Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, −2.9 ± 1.1%; and multiple bursts, −11.0 ± 1.4%; both, P < 0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1 ± 0.5%; P < 0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts.

Download Full-text

Disruption of phase synchronization between blood pressure and muscle sympathetic nerve activity in postural vasovagal syncope

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00415.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. H1238-H1245 ◽

Cited By ~ 12

Author(s):

Christopher E. Schwartz ◽

Elisabeth Lambert ◽

Marvin S. Medow ◽

Julian M. Stewart

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Phase Synchronization ◽

Vasovagal Syncope ◽

Muscle Sympathetic Nerve Activity ◽

Nerve Activity ◽

Control Subjects ◽

Late Stages

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and arterial pressure (AP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA-AP baroreflex entrainment is disrupted before VVS regardless of MSNA withdrawal using the phase synchronization between blood pressure and MSNA during head-up tilt (HUT) to measure reflex coupling. We studied eight VVS subjects and eight healthy control subjects. Heart rate, AP, and MSNA were measured during supine baseline and at early, mid, late, and syncope stages of HUT. Phase synchronization indexes, measuring time-dependent differences between MSNA and AP phases, were computed. Directionality indexes, indicating the influence of AP on MSNA (neural arc) and MSNA on AP (peripheral arc), were computed. Heart rate was greater in VVS compared with control subjects during early, mid, and late stages of HUT and significantly declined at syncope ( P = 0.04). AP significantly decreased during mid, late, and syncope stages of tilt in VVS subjects only ( P = 0.001). MSNA was not significantly different between groups during HUT ( P = 0.700). However, the phase synchronization index significantly decreased during mid and late stages in VVS subjects but not in control subjects ( P < .001). In addition, the neural arc was significantly affected more than the peripheral arc before syncope. In conclusion, VVS is accompanied by a loss of the synchronous AP-MSNA relationship with or without a loss in MSNA at faint. This provides insight into the mechanisms behind the loss of vasoconstriction and drop in AP independent of MSNA at the time of vasovagal faint.

Download Full-text

Abstract 529: Muscle Sympathetic Nerve Activity is Higher in Winter than Other Seasons

Hypertension ◽

10.1161/hyp.62.suppl_1.a529 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Jian Cui ◽

Matthew D Muller ◽

Allen R Kunselman ◽

Cheryl Blaha ◽

Lawrence I Sinoway

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Epidemiological Data ◽

Repeated Measurements ◽

Nerve Activity ◽

Cardiovascular Morbidity And Mortality ◽

Significant Difference

Epidemiological data suggest that blood pressure tends to be higher in winter and lower in summer, particularly in the elderly. Moreover, hospitalization and mortality rates due to cardiovascular disease have higher rates in winter than summer. Whether autonomic adjustment including muscle sympathetic nerve activity (MSNA) varies with season is unclear. To test the hypothesis that resting MSNA varies along the seasons, we retrospectively analyzed the supine baseline (6 min) MSNA and heart rate (from ECG) of 57 healthy subjects (33M, 24F, 29 ± 1 yrs, range 22-64 yrs) from studies in our laboratory (room temperature ~23 °C). Each of these subjects from central Pennsylvania was studied during 2 or more seasons (total 231 visits). A linear-mixed effects model, which is an extension of the analysis of variance model accounting for repeated measurements (i.e. season) per subject, was used to assess the association of season with the cardiovascular outcomes. The Tukey-Kramer procedure was used to account for multiple comparisons testing between the seasons. MSNA burst rate in winter (21.3 ± 1.0 burst/min) was significantly greater than in summer (13.7 ± 1.0 burst/min, P < 0.001), spring (17.5 ± 1.6 burst/min, P = 0.04) and fall (17.0 ± 1.2 burst/min, P < 0.002). There was no significant difference in MSNA in other comparisons (spring vs. summer, P = 0.12; spring vs. fall, P = 0.99; summer vs. fall, P = 0.054). Heart rate (63.6 ± 1.1 vs. 60.8 ± 1.2 beats/min, P = 0.048) was significantly greater in winter compared to summer. Blood pressure (automated sphygmomanometry of the brachial artery) was not significantly different between seasons. The results suggest that baseline sympathetic nerve activity varies along the seasons, with peak levels evident in winter. We speculate that the seasonal MSNA variation may contribute to seasonal variations in cardiovascular morbidity and mortality.

Download Full-text

Influence of Sex and Age on Muscle Sympathetic Nerve Activity of Healthy Normotensive Adults

Hypertension ◽

10.1161/hypertensionaha.120.15208 ◽

2020 ◽

Vol 76 (3) ◽

pp. 997-1005 ◽

Cited By ~ 5

Author(s):

Daniel A. Keir ◽

Mark B. Badrov ◽

George Tomlinson ◽

Catherine F. Notarius ◽

Derek S. Kimmerly ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Body Mass ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Systematic Change ◽

Burst Frequency ◽

Nerve Activity ◽

Age Related

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18–78 years [mean±SD]) and 260 female (age: 37±18; range: 18–81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min −1 ; P <1×10 −19 ; 106±11/66±8 versus 116±7/68±9 mm Hg; P <0.01) but converged thereafter (38±11 versus 35±12 bursts·min −1 ; P =0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P >0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, −4 to 5) and 12 (95% CI, 6–16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women.

Download Full-text

Cardiopulmonary baroreceptor control of muscle sympathetic nerve activity in heat-stressed humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.6.h2348 ◽

1999 ◽

Vol 277 (6) ◽

pp. H2348-H2352 ◽

Cited By ~ 45

Author(s):

C. G. Crandall ◽

R. A. Etzel ◽

D. B. Farr

Keyword(s):

Blood Pressure ◽

Heat Stress ◽

Arterial Blood Pressure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Venous Pressure ◽

Whole Body ◽

Nerve Activity ◽

Arterial Blood

Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7–10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 ± 3 to 39 ± 3 bursts/min ( P < 0.05). Central blood volume expansion via rapid saline infusion did not significantly decrease MSNA (44 ± 4 bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 ± 3 to 93 ± 4 mmHg ( P < 0.05) caused MSNA to decrease from 36 ± 3 to 15 ± 4 bursts/min ( P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.

Download Full-text

Arterial pressure and muscle sympathetic nerve activity are increased after two hours of sustained but not cyclic hypoxia in healthy humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00495.2004 ◽

2005 ◽

Vol 98 (1) ◽

pp. 343-349 ◽

Cited By ~ 31

Author(s):

Renaud Tamisier ◽

Amit Anand ◽

Luz M. Nieto ◽

David Cunnington ◽

J. Woodrow Weiss

Keyword(s):

Blood Pressure ◽

Arterial Pressure ◽

Sympathetic Nerve ◽

Sympathetic Activity ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Arterial Oxygen ◽

Nerve Activity ◽

Arterial Blood ◽

Sustained Hypoxia

Sustained and episodic hypoxic exposures lead, by two different mechanisms, to an increase in ventilation after the exposure is terminated. Our aim was to investigate whether the pattern of hypoxia, cyclic or sustained, influences sympathetic activity and hemodynamics in the postexposure period. We measured sympathetic activity (peroneal microneurography), hemodynamics [plethysmographic forearm blood flow (FBF), arterial pressure, heart rate], and peripheral chemosensitivity in normal volunteers on two occasions during and after 2 h of either exposure. By design, mean arterial oxygen saturation was lower during sustained relative to cyclic hypoxia. Baseline to recovery muscle sympathetic nerve activity and blood pressure went from 15.7 ± 1.2 to 22.6 ± 1.9 bursts/min ( P < 0.01) and from 85.6 ± 3.2 to 96.1 ± 3.3 mmHg ( P < 0.05) after sustained hypoxia, respectively, but did not exhibit significant change from 13.6 ± 1.5 to 17.3 ± 2.5 bursts/min and 84.9 ± 2.8 to 89.8 ± 2.5 mmHg after cyclic hypoxia. A significant increase in FBF occurred after sustained, but not cyclic, hypoxia, from 2.3 ± 0.2 to 3.29 ± 0.4 and from 2.2 ± 0.1 to 3.1 ± 0.5 ml·min−1·100 g of tissue−1, respectively. Neither exposure altered the ventilatory response to progressive isocapnic hypoxia. Two hours of sustained hypoxia increased not only muscle sympathetic nerve activity but also arterial blood pressure. In contrast, cyclic hypoxia produced slight but not significant changes in hemodynamics and sympathetic activity. These findings suggest the cardiovascular response to acute hypoxia may depend on the intensity, rather than the pattern, of the hypoxic exposure.

Download Full-text

Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared with eicosapentaenoic acid in healthy men and women

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00677.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. H873-H881 ◽

Cited By ~ 8

Author(s):

Jordan B. Lee ◽

Karambir Notay ◽

Shannon L. Klingel ◽

Adrian Chabowski ◽

David M. Mutch ◽

...

Keyword(s):

Blood Pressure ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

Olive Oil ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Nerve Activity ◽

Men And Women ◽

Resting Blood Pressure

Supplementation with monounsaturated or ω-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ω-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [−3.4 mmHg (−0.9, −5.9), P = 0.008] and OO [−3.0 mmHg (−0.5, −5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [−3.4 mmHg (−1.3,−5.6), P = 0.002] and OO [−2.2 mmHg (0.08,−4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (−0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [−3 bursts/min (−6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.

Download Full-text