Sympathetic Vascular Transduction Research Articles

Sympathetic Transduction at Rest and During Cold Pressor Test in Young Healthy non-Hispanic Black and White Women.

Non-Hispanic Black (BL) individuals have the highest prevalence of hypertension and cardiovascular disease (CVD) compared to all other racial/ethnic groups. Previous work focused on racial disparities in sympathetic control and blood pressure (BP) regulation between young BL and White (WH) adults, have mainly included men. Herein, we hypothesized that BL women would exhibit augmented resting sympathetic vascular transduction and greater sympathetic and BP reactivity to cold pressor test (CPT) compared to WH women. Twenty-eight young healthy women (BL:n=14, 224 years; WH:n=14, 224 years) participated. Beat-to-beat BP (Finometer), common femoral artery blood flow (duplex Doppler ultrasound), and muscle sympathetic nerve activity (MSNA; microneurography) were continuously recorded. In a subset (BL n=10, WH n=11), MSNA and BP were recorded at rest and during a two-minute CPT. Resting sympathetic vascular transduction was quantified as changes in leg vascular conductance (LVC) and mean arterial pressure (MAP) following spontaneous bursts of MSNA using signal-averaging. Sympathetic and BP reactivity was quantified as changes in MSNA and MAP during the last minute of CPT. There were no differences in nadir LVC following resting MSNA bursts between BL (-8.74±3.45%) and WH women (-7.48±3.52%; P=0.431). Likewise, peak increases in MAP following MSNA bursts were not different between groups (BL:+2.80+1.4mmHg; vs. WH: +3.02±1.2mmHg; P=0.623). During CPT, increases in MSNA and MAP were also not different between BL and WH women, with similar transduction estimates between groups (ΔMAP/ΔMSNA; P=0.182). These findings indicate that young, healthy BL women do not exhibit exaggerated sympathetic transduction or augmented sympathetic and BP reactivity during CPT.

The effects of biological sex and oral contraception on the sympathetic neurocirculatory adjustments to static handgrip exercise in humans.

Biological sex affects the neurocirculatory adjustments to fatiguing exercise. However, the effects of sex and oral contraceptive pills (OCPs) on sympathetic action potential (AP) emission patterns and the transduction of AP discharge into vasoconstriction during static handgrip (SHG) exercise remains unknown. We tested the hypothesis that males, and females using OCPs, would demonstrate larger increases in sympathetic activation and sympathetic vascular transduction compared to naturally menstruating females during SHG and post-exercise circulatory occlusion (PECO). Young males (n=14, 25[5] yr), females using OCPs (n=16, 24[6] yr), and naturally menstruating females (n=18, 26[4] yr) underwent assessments of multi-unit muscle sympathetic nerve activity (MSNA)/AP discharge patterns (microneurography), and femoral artery blood flow (ultrasound) during fatiguing SHG at 40% maximum voluntary contraction and 2-min PECO. Sympathetic vascular transduction was determined as the quotient of the change in leg vascular conductance (LVC) and MSNA/AP discharge. Males demonstrated greater increases in APs/burst (P=0.028) and total AP clusters (P=0.008) compared to naturally menstruating females only, but not those using OCPs during exercise. Sympathetic vascular transduction of MSNA burst amplitude, APs/burst, and total AP clusters was greater in males and females using OCPs compared to naturally menstruating females (range: P=0.004-0.044). In contrast, no group differences in AP discharge were observed during PECO (range: P=0.510-0.872), and AP discharge was not related to LVC during PECO (range: P=0.08-0.949). These data indicate that biological sex and OCP use impact the central generation of efferent AP discharge, as well as the transduction of these neuronal messages into peripheral vasoconstriction during static exercise.

Age- and sex-related differences in sympathetic vascular transduction and neurohemodynamic balance in humans.

Bursts of muscle sympathetic nerve activity (MSNA) and the ensuing vasoconstriction are pivotal determinants of beat-by-beat blood pressure regulation. Although age and sex impact blood pressure regulation, how these factors affect the central and peripheral arcs of the baroreflex remains unclear. In 27 young [25 (SD 3) yr] males (YM; n = 14) and females (YF; n = 13) and 23 older [71 (SD 5) yr] males (OM; n = 11) and females (OF; n = 12), femoral artery blood flow, blood pressure, and MSNA were recorded for 10 min of supine rest. Sympathetic baroreflex sensitivity (i.e., central arc) was quantified as the relationship between diastolic blood pressure and MSNA burst incidence. Signal averaging was used to determine sympathetic vascular transduction into leg vascular conductance (LVC) for 12 cardiac cycles following MSNA bursts (i.e., peripheral arc). Older adults demonstrated attenuated sympathetic transduction into LVC (both P < 0.001) following MSNA bursts, and smaller increases in sympathetic transduction as a function of MSNA burst size and firing pattern compared with young adults (range, P = 0.004-0.032). YM (r2 = 0.36; P = 0.032) and OM (r2 = 0.51; P = 0.014) exhibited an inverse relationship between the central and peripheral arcs of the baroreflex, whereas females did not (YF, r2 = 0.03, P = 0.621; OF, r2 = 0.06, P = 0.445). MSNA burst incidence was inversely related to sympathetic transduction in YM and OF (range, P = 0.03-0.046) but not in YF or OM (range, P = 0.360-0.603). These data indicate that age is associated with attenuated sympathetic vascular transduction, whereas age- and sex-specific changes are present in the relationship between the central and peripheral arcs of the baroreflex regulation of blood pressure.NEW & NOTEWORTHY Sympathetic vascular transduction is attenuated in older compared with young adults, regardless of biological sex. Males, but not females (regardless of age), demonstrate an inverse relationship between central (sympathetic baroreflex sensitivity) and peripheral (sympathetic vascular transduction) components of the baroreflex arc. Young males and older females exhibit an inverse relationship between resting sympathetic outflow and sympathetic vascular transduction. Our results indicate that age and sex exert independent and interactive effects on sympathetic vascular transduction and sympathetic neurohemodynamic balance in humans.

Sympathetic reactivity and inflammation: another joint problem in rheumatoid arthritis?

Sympathetic reactivity and inflammation: another joint problem in rheumatoid arthritis?

Sympathetic Vascular Transduction is Elevated in Hypertensive Premenopausal and Postmenopausal Women

The transduction of muscle sympathetic nerve activity (MSNA) to vasoconstrictor tone is lower in healthy young women versus both healthy young men and healthy postmenopausal women, and may account for the lower risk of hypertension in young women. However, hypertension can occur before menopause in some women but whether sympathetic transduction is increased in this group is unknown. We aimed to determine whether sympathetic transduction is different in hypertensive (HTN) pre‐ and post‐menopausal women relative to normotensive (NTN) controls. MSNA (peroneal microneurography) and continuous blood pressure (Finometer Pro) were measured in HTN (n=5) and NTN (n=5) premenopausal and HTN (n=4) and NTN (n=6) postmenopausal women. HTN and NTN groups were matched for age (premenopausal; 46±2 vs. 46±5 years, p=0.97, postmenopausal; 59±4 vs. 62 ±2 years; p=0.17). Sympathetic transduction was measured by associating beat‐to‐beat diastolic blood pressure (DBP) with MSNA burst area between the 6th and 8th previous cardiac cycles to account for transduction delay. Transduction was expressed as the slope of the linear regression between burst area and mean DBP, plotted as 1 %.s bins. HTN and NTN were compared within pre‐ or postmenopausal groups by unpaired Student’s T‐test or Mann‐Whitney test, where data were not normally distributed. Data are presented as mean ± SD. Both sympathetic transduction and MSNA were greater in HTN versus NTN premenopausal women (0.16±0.11 vs. 0.03±0.02 mmHg/%.s, p=0.03; 57±17 vs. 32±7 bursts/100 heartbeats, p=0.0185). Sympathetic transduction was also greater in HTN vs. NTN postmenopausal women (0.19±0.08 vs. 0.07±0.02 mmHg/%.s, p=0.02), although MSNA was similar (53±8 vs. 60±15 bursts/100 heartbeats, p=0.4255). Both HTN groups had increased clinic systolic BP and DBP versus the respective NTN group (premenopausal women 153±11/97±6 vs. 119±9/73±8 mmHg, p=0.0007 and p=0.0079; postmenopausal women 155±8/92±15 vs. 123±8/70±7 mmHg, p=0.0095 and p=0.0132 respectively). These results indicate that sympathetic transduction is elevated in both premenopausal and postmenopausal women with HTN vs. NTN controls. As such, increased sympathetic transduction may help to explain the development of hypertension in premenopausal women. These data will assist with more precise management of hypertension in pre‐ and postmenopausal women.Support or Funding InformationZoe Adams is funded by a British Heart Foundation Non‐Clinical PhD Studentship (FS/17/38/32935).

The Potential Impact of Discrete Action Potentials on Resting Sympathetic Vascular Transduction in Humans

The sympathetic nervous system dynamically regulates blood pressure (BP), primarily through the modification of peripheral vascular tone. Our lab has developed a methodology for quantifying resting sympathetic vascular transduction wherein bursts of muscle sympathetic nerve activity (MSNA) act as a trigger and ensuing changes in BP and vascular conductance are signal‐averaged over the subsequent 15 cardiac cycles to produce characteristic (mean) responses. These previous investigations have focused on the effect of net sympathetic outflow (e.g, burst sequences and burst amplitudes) on the pressor and vascular conductance responses to spontaneous bursts of MSNA. The recent development of methods to identify sympathetic action potentials (APs) to obtain further information regarding sympathetic control of the circulation has led us to begin to examine the potential role that discrete sympathetic APs may play in determining the BP and vascular responses following spontaneous bursts of MSNA. Herein, we compared BP and leg vascular conductance responses between MSNA bursts containing small (i.e., common) or large (i.e., uncommon) APs within quartiles of MSNA normalized to burst amplitude. We hypothesized the presence of large APs in a burst of MSNA would elicit a greater pressor response and a larger decrease in leg vascular conductance. Resting MSNA (microneurography), beat‐to‐beat BP (finger photoplethysmography), and femoral artery blood velocity (Doppler ultrasound) were collected for 10–20 minutes in 5 young healthy adults. Leg vascular conductance index was calculated (LVCi=femoral artery blood velocity/mean arterial pressure). MSNA bursts were sorted into normalized amplitude quartiles (Q1=smallest 25% of bursts; Q4=largest 25% of bursts), and APs were extracted using a matched wavelet methodology. Within Q4, there was no difference in the peak BP or LVCi responses to bursts containing small APs when compared to bursts containing large APs (Δ6±3 small vs. Δ6±2 large mmHg, p=0.74; Δ0.95±2.0 small vs. Δ0.87±1.7 large ml·min−1·mmHg−1, p=0.59). To account for the potential contribution of MSNA bursts occurring in consecutive sequence, we next isolated singlet bursts (separated by ≥1 cardiac cycle lacking MSNA bursts). Within Q4, there was again no difference in the peak BP or LVCi response to singlet bursts containing small APs compared to singlet bursts containing large APs (Q4: Δ7±3 small vs. Δ6±2 large mmHg, p=0.42; Δ0.05±0.07 small vs. Δ0.17±0.11 large ml·min−1·mmHg−1, p=0.08). These preliminary data suggest that the presence of large APs does not appear to translate to greater pressor or decreased leg vascular conductance responses following a spontaneous burst of resting MSNA.Support or Funding InformationFunded by the UTA College of Nursing and Health Innovation and Natural Sciences and Engineering Research Council of Canada

Neural control of cardiovascular function in black adults: implications for racial differences in autonomic regulation.

Black adults are at increased risk for developing hypertension and cardiovascular and chronic kidney disease and have greater associated morbidity/mortality than white adults who are otherwise demographically similar. Despite the key role of the autonomic nervous system in the regulation of cardiovascular function, the mechanistic contributions of sympathetic nerves to racial differences in cardiovascular dysfunction and disease remain poorly understood. In this review, we present an update and synthesis of current understanding regarding the roles of autonomic neural mechanisms in normal and pathophysiological cardiovascular control in black and white adults. At rest, many hemodynamic and autonomic variables, including blood pressure, cardiac output, and sympathetic nerve activity, are similar in healthy black and white adults. However, resting sympathetic vascular transduction and carotid baroreflex responses are altered in ways that tend to promote increased vasoconstriction and higher blood pressure, even in healthy, normotensive black adults. Acute sympathoexcitatory maneuvers, including exercise and cold pressor test, often result in augmented sympathetic and hemodynamic responses in healthy black adults. Clinically, although mechanistic evidence is scarce in this area, existing data support the idea that excessive sympathetic activation and/or transduction into peripheral vasoconstriction contribute importantly to the pathophysiology of hypertension and chronic kidney disease in black compared with white adults. Important areas for future work include more detailed study of sympathetic and hemodynamic reactivity to exercise and other stressors in male and female black adults and, particularly, sympathetic control of renal function, an important area of clinical concern in black patients.

Short-term water deprivation does not increase blood pressure variability or impair neurovascular function in healthy young adults.

High dietary salt increases arterial blood pressure variability (BPV) in salt-resistant, normotensive rodents and is thought to result from elevated plasma [Na+] sensitizing central sympathetic networks. Our purpose was to test the hypothesis that water deprivation (WD)-induced elevations in serum [Na+] augment BPV via changes in baroreflex function and sympathetic vascular transduction in humans. In a randomized crossover fashion, 35 adults [17 female/18 male, age: 25 ± 4 yr, systolic/diastolic blood pressure (BP): 107 ± 11/60 ± 7 mmHg, body mass index: 23 ± 3 kg/m2] completed two hydration protocols: a euhydration control condition (CON) and a stepwise reduction in water intake over 3 days, concluding with 16 h of WD. We assessed blood and urine electrolyte concentrations and osmolality, resting muscle sympathetic nerve activity (MSNA; peroneal microneurography; 18 paired recordings), beat-to-beat BP (photoplethysmography), common femoral artery blood flow (Doppler ultrasound), and heart rate (single-lead ECG). A subset of participants (n = 25) underwent ambulatory BP monitoring during day 3 of each protocol. We calculated average real variability as an index of BPV. WD increased serum [Na+] (141.0 ± 2.3 vs. 142.1 ± 1.7 mmol/L, P < 0.01) and plasma osmolality (288 ± 4 vs. 292 ± 5 mosmol/kg H2O, P < 0.01). However, WD did not increase beat-to-beat (1.9 ± 0.4 vs. 1.8 ± 0.4 mmHg, P = 0.24) or ambulatory daytime (9.6 ± 2.1 vs. 9.4 ± 3.3 mmHg, P = 0.76) systolic BPV. Additionally, sympathetic baroreflex sensitivity (P = 0.20) and sympathetic vascular transduction were not different after WD (P = 0.17 for peak Δmean BP following spontaneous MSNA bursts). These findings suggest that, despite modestly increasing serum [Na+], WD does not affect BPV, arterial baroreflex function, or sympathetic vascular transduction in healthy young adults.

Exaggerated Alpha‐1 Adrenoreceptor Mediated Vasoconstriction in Young Black Men is not Influenced by Superoxide‐Mediated Oxidative Stress

Black individuals (BL) have a greater risk for hypertension and cardiovascular disease than other populations, the cause of which is likely multifactorial. However, vascular dysfunction appears to be a key preceding factor to the racial disparities observed. This observation has been demonstrated in young, otherwise healthy BL. Our group recently demonstrated that young BL men (BM) exhibit exaggerated sympathetic vascular transduction (SVT), i.e., greater vasoconstriction and pressor responses to spontaneous bursts of sympathetic nerve activity, at rest compared to young white men (WM). This response may be mediated by elevated oxidative stress, which may be 1) reducing nitric oxide (NO) bioavailability and subsequent vasodilatory capacity and/or 2) directly affecting blood vessel reactivity. In this regard, previous literature has established that young BM have elevated oxidative stress and reduced NO bioavailability relative to other populations. Whether these conditions contribute to increased SVT in BM is currently unknown. Accordingly, this study tested the hypothesis that BM have an exaggerated vasoconstrictor response to the selective α1‐adrenoreceptor agonist phenylephrine (PE) compared to WM which is augmented by elevated oxidative stress. To test this hypothesis, four intradermal microdialysis membranes were placed in the dorsal forearm of 3 WM and 6 BM (mean ± SD; age: 24±5 vs. 22±3 y) and the skin blood flow (SkBF) responses to intradermal infusion of PE were assessed. Following trauma resolution, each site received one of four infusions for 30‐min: lactated Ringer's (control), apocynin (NADPH oxidase inhibitor; 100 μM), allopurinol (xanthine oxidase inhibitor; 10 μM), or tempol (superoxide scavenger; 10 μM). Each site was then locally heated to 33°C for 10‐min to establish baseline SkBF. Each site then received a coinfusion of PE (100 mM) for 6‐min to elicit vasoconstriction, with the response presented as a percent reduction in cutaneous vascular conductance (CVC; flux/mean arterial pressure) from baseline (%CVCB). Following PE administration, BM exhibited exaggerated vasoconstriction compared to WM (control: −69.0±16.5 vs. −34.8±15.2 %CVCB; apocynin: −58.1±18.3 vs. −43.5± 2.4 %CVCB; allopurinol: −59.2±13.1 vs. −53.5±23.3 %CVCB; tempol: −63.5±18.1 vs. −37.7±16.7 %CVCB; main effect: P &lt; 0.01). However, no interaction effect was observed for the race‐by‐site comparison (P = 0.35), suggesting no effect of the drugs used across races. In conclusion, these preliminary data suggest that BM exhibit exaggerated α1‐adrenoreceptor‐mediated vasoconstriction compared to WM, which is consistent with previous literature. Furthermore, these preliminary findings indicate this response is not superoxide‐mediated, suggestive of a different, currently unknown controlling mechanism for exaggerated vasoconstriction.Support or Funding InformationUTA Start‐up funds to R. Matthew BrothersThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impaired Baroreflex Function during Rest and Graded Orthostasis in Women with PTSD

Post‐traumatic stress disorder (PTSD) is more prevalent in women and associated with significantly higher risk of hypertension and cardiovascular disease. The underlying mechanisms are unclear, but impaired baroreflex function and vasomotor sympathetic neural control may be involved. We hypothesized that women with PTSD would have an impaired baroreflex control of muscle sympathetic nerve activity (MSNA). MSNA and hemodynamics were measured supine and during 30º and 60º head‐up tilt (HUT) in 14 women with PTSD and 14 healthy women (Controls). Sympathetic baroreflex sensitivity(BRS) was quantified using the slope of the linear correlation between MSNA and diastolic pressure during spontaneous breathing. Age and body mass index were not different between groups. Supine resting MSNA was greater in women with PTSD (PTSD vs. Controls: 27±3 vs. 14±3 bursts/min; P=0.002, mean±SEM). Sympathetic BRS was impaired in women with PTSD compared to controls in the supine position (PTSD vs. Controls: −43±7 vs. −64±9 units 100beats−1 mmHg−1, P=0.02). It remained lower in women with PTSD during 30º and 60º HUT (posturexgroup interaction P=0.1, time P=0.003, group P=0.03). MSNA response to the graded HUT was not different between groups but the efficacy of MSNA for vasoconstriction was greater in women with PTSD (HUT 30: 1.8±0.5 vs.0.9±0.4 %TPR/%totalMSNA; P=0.01, HUT60: 1.2±0.4 vs. 0.7±0.3; P=0.04). Our findings demonstrate that women with PTSD have decreased sympathetic BRS and it may contribute to augmented sympathetic activity. The higher efficacy of MSNA for vasoconstriction in PTSD suggests greater sympathetic vascular transduction and/or other nonadrenergic mechanisms responsible for vasoconstriction. These results may explain, in part, the underlying mechanisms for the greater risk of developing hypertension and cardiovascular disease in women with PTSD.Support or Funding InformationSupported by the Harry S. Moss Heart TrustThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Role of Muscle Metaboreflex in the Reduced Blood Pressure Response to Exercise in Patients Living with HIV

The cardiovascular adjustments during exercise are regulated by several neural mechanisms working in concert, including the muscle metaboreflex. The response to this reflex could be involved in the reduced diastolic blood pressure observed in HIV patients during exercise. However, this hypothesis has not been tested yet. Thus, 18 patients living with HIV (46±10 yr, mean ±SD; 16 men; HIV group) and 13 control subjects (41±8 yr; 10 men; Control group) were evaluated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiac output and total vascular resistance were calculated using photoplethysmography and Model flow method. Cardiac index (CI) and total vascular resistance index (TVRI) were corrected by body surface area. SBP and DBP was recorded during 3 minutes of rest, followed by 3 minutes of isometric handgrip exercise at 30% of their maximal voluntary force and 2 minutes of post exercise ischemia to isolate muscle metaboreflex activation. Data were subject to two‐way ANOVA followed by multiple comparisons with Bonferroni correction. SBP increased during exercise (Control: Δ22±6 mmHg vs. HIV: Δ17±8 mmHg) and during metaboreflex activation in both groups (1st min: Control: Δ12±6 mmHg vs. HIV: Δ8±5 mmHg; 2nd min: Control: Δ15±8 mmHg vs. HIV: Δ12±9 mmHg). However, DBP response to exercise was attenuated in HIV patients (Control: Δ16±5 mmHg vs. HIV: Δ10±4 mmHg). This difference remained during metaboreflex activation (1st min: Control: Δ9±5 mmHg vs. HIV: Δ3±2 mmHg; 2nd min: Control: Δ11±6 mmHg vs. HIV: Δ6±4 mmHg). TVRI increased during exercise only in the control group (Control: Δ1.31±0.79 mmHg.min/l vs. HIV: Δ0.28±1.60 mmHg.min/l) and remained elevated during metaboreflex activation. In contrast, a decrease of the TVRI during the 1st minute of the metaboreflex activation (Control: Δ1.43±0.69 mmHg.min/l vs. HIV: Δ0.22±1.22 mmHg.min/l) and a blunted increase at the 2nd minute was observed in HIV patients (Control: Δ1.56±1.04 mmHg.min/l vs. HIV: Δ0.84±1.25 mmHg.min/l). CI increased during exercise (Control: Δ0.43±0.57 l/min vs. HIV: Δ0.42±0.32 l/min) and decreased during metaboreflex activation in both groups (1st min: Control: Δ0.07±0.32 l/min vs. HIV: Δ0.15±0.25 l/min; 2nd min: Control: Δ0.16±0.42 l/min vs. HIV: Δ 0.13±0.25 l/min). HR increased during exercise (Control: Δ9±6 bpm vs. HIV: Δ8±4 bpm) and returned to resting values during metaboreflex activation in both groups (1st min: Control: Δ‐1±2 bpm vs. HIV: Δ0±3 bpm; 2nd min: Control: Δ0±3 bpm vs. HIV: Δ0±4 bpm). In conclusion, seems that patients living with HIV present blunted peripheral vasoconstriction response to metaboreflex activation, which explain the reduced diastolic blood pressure response to exercise, already observed in these patients. We believe that a lower sympathetic activation and/or deficient sympathetic vascular transduction are the two possible mechanisms driving the response.Support or Funding InformationFAPERJ, CAPES and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Reducing Dietary Sodium to 1000 mg per Day Reduces Neurovascular Transduction Without Stimulating Sympathetic Outflow.

The American Heart Association recommends no more than 1500 mg of sodium/day as ideal. Some cohort studies suggest low-sodium intake is associated with increased cardiovascular mortality. Extremely low-sodium diets (≤500 mg/d) elicit activation of the renin-angiotensin-aldosterone system and stimulate sympathetic outflow. The effects of an American Heart Association-recommended diet on sympathetic regulation of the vasculature are unclear. Therefore, we assessed whether a 1000 mg/d diet alters sympathetic outflow and sympathetic vascular transduction compared with the more commonly recommended 2300 mg/d. We hypothesized that sodium reduction from 2300 to 1000 mg/d would not affect resting sympathetic outflow but would reduce sympathetic transduction in healthy young adults. Seventeen participants (age: 26±2 years, 9F/8M) completed 10-day 2300 and 1000 mg/d sodium diets in this randomized controlled feeding study (crossover). We measured resting renin activity, angiotensin II, aldosterone, blood pressure, muscle sympathetic nerve activity, and norepinephrine. We quantified beat-by-beat changes in mean arterial pressure and leg vascular conductance (femoral artery ultrasound) following spontaneous sympathetic bursts to assess sympathetic vascular transduction. Reducing sodium to 1000 mg/d increased renin activity, angiotensin II, and aldosterone ( P<0.01 for all) but did not alter mean arterial pressure (78±2 versus 77±2 mm Hg, P=0.56), muscle sympathetic nerve activity (13.9±1.3 versus 13.9±0.8 bursts/min, P=0.98), or plasma/urine norepinephrine. Sympathetic vascular transduction decreased ( P<0.01). These data suggest that reducing sodium from 2300 to 1000 mg/d stimulates the renin-angiotensin-aldosterone system, does not increase resting basal sympathetic outflow, and reduces sympathetic vascular transduction in normotensive adults.

Greater Beat‐To‐Beat Resting Blood Pressure Variability in Young Healthy African American Men

It is well documented that African Americans (AA) are at a greater risk for the development of hypertension than Caucasian Americans (CA). Our laboratory has recently demonstrated exaggerated transduction of sympathetic nerve activity to blood pressure (BP) in young, healthy AA men compared to CA men. The influence of this greater sympathetic vascular transduction on BP variability is unclear. Although previous studies have reported greater BP variability in AA than CA based on 24‐hr ambulatory BP measurements, to date, no studies have investigated resting BP variability on a beat‐to‐beat basis in AA. Thus, we tested the hypothesis that young AA men would exhibit greater beat‐to‐beat BP variability in comparison to CA men. Heart rate (ECG), and beat‐to‐beat arterial BP (finger photoplethysmography) were continuously measured during a 20‐minute resting period in young, healthy CA (n=15) and AA (n=14) men. The arterial BP waveform was analyzed via Modelflow to estimate stroke volume, and used to calculate cardiac output (CO) and total peripheral resistance [TPR: mean arterial pressure (MAP) divided by CO]. Variance, range, and interquartile range were calculated for MAP, CO and TPR. Data are presented as mean ± standard error (SE). Despite similar average absolute resting systolic BP, diastolic BP, and MAP, compared to CA, AA exhibited larger MAP variance (CA: 19.2±2.6 mmHg2, AA: 32.3±4.0 mmHg2, p=0.009). In addition, the range (CA: 26.9±2.0 mmHg; AA: 33.2±1.8 mmHg, p=0.03) and interquartile range (CA: 5.7±0.4 mmHg; AA: 7.6±0.5 mmHg, p=0.007) of MAP were greater in AA than CA. Similar results were found for both systolic BP and diastolic BP. Interestingly, the variance of CO was not significantly different between groups (P=0.63), whereas the variance of TPR was significantly greater in AA than CA (P=0.03). Likewise, the TPR (but not CO) range, and interquartile range were greater in AA than CA. These findings demonstrate that, relative to CA, AA exhibit greater beat‐to‐beat BP variability which appears to be related to greater variability in TPR. Overall, these greater fluctuations in resting BP may constitute a source of future cardiovascular risk in AA men, and predispose them to the development of hypertension.Support or Funding InformationSupported by NIH R15 HL130906.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Methodological assessment of sympathetic vascular transduction.

Methodological assessment of sympathetic vascular transduction.

Acute oral ingestion of alcohol modulates muscle sympathetic neural activity differently in Caucasians and African Americans

Recent studies consistently report that acute alcohol consumption increases muscle sympathetic nerve activity (MSNA) in humans. Despite the increased prevalence of hypertension and alcohol consumption in African Americans (AA), no studies have compared MSNA responses to alcohol consumption in AA and Caucasians (C). We hypothesized that alcohol consumption would increase MSNA in both AA and C, but that sympathoexcitatory responses would be augmented in AA. Five minutes of supine heart rate (HR), blood pressure, MSNA, and forearm blood flow were recorded in 8 AA (age, 23±1 yr) and 8 C (age, 22±1 yr) before and 45 min after consumption of 2.5ml of vodka per kg body mass. Increases in blood alcohol content (BAC) were greater in AA (0.105%) compared to C (0.087%; P&lt;0.05). Alcohol elicited similar increases of HR in AA (62±5 to 70±4 beats/min; p&lt;0.001) and C (62±5 to 68±5 beats/min; p&lt;0.001). Contrary to our initial hypothesis, alcohol consumption increased MSNA in C (14±3 to 27±5 bursts/100 heart beats; P&lt;0.05), but did not alter MSNA in AA (28±7 to 29±6 bursts/100 heart beats). Forearm vascular conductance (FVC) was not altered by alcohol consumption in AA or C. However, when sympathetic vascular transduction was calculated (i.e., FVC/MSNA), alcohol consumption reduced sympathetic vascular transduction in C (2.4±0.4 to 1.1±0.2 units; p&lt;0.01), but not AA (1.3±0.4 to 1.3±0.4 units). These findings suggest acute alcohol consumption influences resting MSNA and MSNA‐vascular coupling differently in AA and C, but it is unclear if the different levels of BAC, and perhaps rates of alcohol metabolism, are contributing to these racial differences.

Obesity and neural cardiovascular responses to mental stress in humans

The relationship between body mass index (BMI) and reactivity to mental stress remains inconclusive in humans. We tested the hypothesis that obese individuals (BMI > 30 kg/m2) would demonstrate augmented neural and cardiovascular responses to mental stress when compared to normal weight (BMI < 25 kg/m2) individuals. Heart rate (HR), mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA) were simultaneously recorded during 5 min of mental stress (via mental arithmetic) in 26 normal weight (age 24±2 yr; BMI 22±0 kg/m2) and 14 obese (age 29±2 yr; BMI 34±1 kg/m2) participants. Resting MAP was higher (p<0.01) in obese (89±2 mmHg) vs. normal weight participants (77±1 mmHg), while resting HR and MSNA were similar between groups. Perceived stress (2.5±0.2 vs. 2.6±0.1 units) and HR (Δ17±2 vs. Δ18±2 beats/min) responses to mental stress were similar for the normal weight and obese, respectively. The MAP response to mental stress was augmented (p<0.05) in the obese (Δ15±2 mmHg) compared to normal weight (Δ11±1 mmHg). In contrast, the MSNA responses to mental stress were blunted (p<0.05) in the obese (Δ1±2 bursts/min) compared to normal weight (Δ5±1 bursts/min). In conclusion, obesity is associated with an augmented MAP reactivity to mental stress, but this augmentation was associated with a paradoxical reduction of MSNA reactivity. Future work might be aimed at replicating the augmented MAP reactivity in obese participants, and examining sympathetic vascular transduction and other potential mechanisms.

Neurovascular control following small muscle-mass exercise in humans.

Sustained postexercise vasodilation, which may be mediated at both a neural and vascular level, is seen in previously active skeletal muscle vascular beds following both large and small muscle-mass exercise. Blunted sympathetic vascular transduction and a downward resetting of the arterial baroreflex contribute to this vasodilation after cycling (large muscle-mass exercise), but it is unknown if these responses also contribute to sustained vasodilation following small muscle-mass exercise. This study aimed to determine if baroreflex sensitivity is altered, the baroreflex is reset, or if sympathetic vascular transduction is blunted following small muscle-mass exercise. Eleven healthy, college-aged subjects (five males, six females) completed one-leg dynamic knee-extension exercise for 1 h at 60% of peak power output. While cardiovagal baroreflex sensitivity was increased ∼23% postexercise relative to preexercise (P < 0.05), vascular and integrated baroreflex sensitivity were not altered following exercise (P = 0.31 and P = 0.48). The baroreflex did not exhibit resetting (P > 0.69), and there was no evidence of changes in vascular transduction following exercise (P = 0.73). In conclusion, and in contrast to large muscle-mass exercise, it appears that small muscle-mass exercise produces a sustained postexercise vasodilation that is largely independent of central changes in the baroreflex.

Neurovascular control following small muscle mass exercise in humans (1170.10)

Sympathetic vascular transduction is blunted and the arterial baroreflex curve is reset to a lower operating pressure after dynamic large muscle mass exercise in humans. It is unknown whether these neural adaptations contribute to sustained post‐exercise vasodilation in small muscle mass exercise. The purpose of this study was to determine if cardiovagal, vascular, and integrated baroreflex sensitivity as well as sympathetic neurovascular transduction were altered following dynamic knee extension (DKE) exercise. It was hypothesized that sympathetic vascular transduction would be reduced after DKE, the arterial baroreflex would be reset to a lower operating point, and baroreflex sensitivity would be enhanced. Eleven healthy, college‐aged subjects completed one‐leg DKE exercise for one hour at 60% of peak power. Neurovascular transduction was estimated by measuring the percent change in femoral vascular conductance due to external neck pressure. There was no effect of exercise on transduction (P = 0.46) and no difference in integrated baroreflex sensitivity across time (P = 0.77). Cardiovagal baroreflex sensitivity increased 25% relative to baseline and had not recovered at 60 minutes post‐exercise (P = 0.02). Vascular baroreflex sensitivity was reduced in both the exercised (P = 0.05) and rested leg (P = 0.09). There is likely no effect of small muscle mass exercise on postexercise sympathetic transduction, the carotid baroreflex, or integrated baroreflex sensitivity. Cardiovagal baroreflex sensitivity was augmented and vascular baroreflex sensitivity was reduced after exercise and this has not been previously shown after small muscle mass exercise.Grant Funding Source: NIH R01 HL115027

The role of α‐adrenergic receptors in mediating beat‐by‐beat sympathetic vascular transduction in the forearm of resting man

Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P = 0.016) and then robustly decreased to a nadir of -5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (-2.1 ± 0.7% and -0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors.

The role of α‐adrenergic receptors in mediating beat‐by‐beat sympathetic vascular transduction in resting humans

Sympathetic vascular transduction is commonly understood to act as a basic relay, but under basal conditions competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC). In 7 young men, MSNA (microneurography) and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during 20 minute infusions of intra‐arterial saline (control), phentolamine (PHEN), and PHEN with angiotensin II (PHEN‐ANG). The latter was used to control for increases in resting blood flow with a‐adrenergic blockade. Signal averaging was used to characterize beat‐by‐beat changes in FVC for 15 cardiac cycles following each individual MSNA burst and a peak response was calculated. During saline, FVC initially increased by +3.3±0.3% following MSNA bursts (P=0.016) and then robustly decreased to a nadir of −5.8±1.5% (P&lt;0.001). PHEN and PHEN+ANG infusion did not alter the initial rise in FVC, but significantly attenuated the ensuing decrease in FVC (−2.1±0.7% and −0.7±0.8%, respectively; P&lt;0.001 vs. saline). These findings indicate that spontaneous MSNA bursts are capable of evoking robust decreases in FVC that are exclusively mediated via α‐adrenergic receptors. Supported by RO1 HL093167