Neurogenic-nitric oxide interactions affecting brachial artery mechanics in humans: roles of vessel distensibility vs. diameter

The purpose of this investigation was to assess the interactive influence of sympathetic activation and supplemental nitric oxide (NO) on brachial artery distensibility vs. its diameter. It was hypothesized that 1) sympathetic activation and NO competitively impact muscular conduit artery (brachial artery) mechanics, and 2) neurogenic constrictor input affects conduit vessel stiffness independently of outright changes in conduit vessel diastolic diameter. Lower body negative pressure (LBNP) and a cold pressor stress (CPT) were used to study the changes in conduit vessel mechanics when the increased sympathetic outflow occurred with and without changes in heart rate (LBNP −40 vs. −15 mmHg) and blood pressure (CPT vs. LBNP). These maneuvers were performed in the absence and presence of nitroglycerin. Neither LBNP nor CPT altered brachial artery diastolic diameter; however, distensibility was reduced by 25 to 54% in each reflex (all P < 0.05). This impact of sympathetic activation on brachial artery distensibility was not altered by nitroglycerin supplementation (21–54%; P < 0.05), although baseline diameter was increased by the exogenous NO ( P < 0.05). The results indicate that sympathetic excitation can reduce the distensibility of the brachial artery independently of concurrent changes in diastolic diameter, heart rate, and blood pressure. However, exogenous NO did not minimize or reverse brachial stiffening during sympathetic activation. Therefore, sympathetic outflow appears to impact the stiffness of this conduit vessel rather than its diastolic diameter or, by inference, its local resistance to flow.

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Characterization of the role of endogenous nitric oxide in myogenic vascular oscillations during cooling-evoked hemodynamic perturbations of rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0476 ◽

2017 ◽

Vol 95 (7) ◽

pp. 803-810 ◽

Cited By ~ 3

Author(s):

Yi-Hsien Lin ◽

Yia-Ping Liu ◽

Yu-Chieh Lin ◽

Po-Lei Lee ◽

Che-Se Tung

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Heart Rate ◽

Cold Stress ◽

Low Frequency ◽

Sympathetic Activation ◽

Nitric Oxide Synthase Inhibitor ◽

Dicrotic Notch ◽

Endogenous Nitric Oxide

Rapid immersion of a rat’s limbs into 4 °C water, a model of cold stress, can elicit hemodynamic perturbations (CEHP). We previously reported that CEHP is highly relevant to sympathetic activation and nitric oxide production. This study identifies the role of nitric oxide in CEHP. Conscious rats were pretreated with the nitric oxide synthase inhibitor L-NAME (NG-nitro-l-arginine methyl ester) alone or following the removal of sympathetic influences using hexamethonium or guanethidine. Rats were then subjected to a 10 min cold-stress trial. Hemodynamic indices were telemetrically monitored throughout the experiment. The analyses included measurements of systolic blood pressure; heart rate; dicrotic notch; short-term cardiovascular oscillations and coherence between blood pressure variability and heart rate variability in regions of very low frequency (0.02–0.2 Hz), low frequency (0.2–0.6 Hz), and high frequency (0.6–3.0 Hz). We observed different profiles of hemodynamic reaction between hexamethonium and guanethidine superimposed on L-NAME, suggesting an essential role for a functional adrenal medulla release of epinephrine under cold stress. These results indicate that endogenous nitric oxide plays an important role in the inhibition of sympathetic activation and cardiovascular oscillations in CEHP.

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Endothelial Function In Tanzanian Children With Sickle Cell Disease: Baseline Results From The Vascular Function Intervention Trial (VFIT)

Blood ◽

10.1182/blood.v122.21.984.984 ◽

2013 ◽

Vol 122 (21) ◽

pp. 984-984

Author(s):

Sharon E. Cox ◽

Julie Makani ◽

Elizabeth Ellins ◽

Gurishaeli Walter ◽

Selemani Mtunguja ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Endothelial Function ◽

Sickle Cell ◽

Brachial Artery ◽

Vascular Function ◽

Full Blood Count ◽

Intervention Trial ◽

Brachial Artery Diameter ◽

Baseline Diameter

Abstract Introduction Endothelial function is impaired in adults with sickle cell anaemia (SCA), but limited data exists in children. Endothelial damage occurs from chronic inflammation, oxidant damage, immune cell activation and ischemia-reperfusion injury. In addition, availability of nitric oxide (NO) as the major vasodilator may be reduced as a result of scavenging by plasma haemoglobin and reduced arginine substrate for endothelial nitric oxide synthase. Methods Tanzanian children (N=119) with SCA (HbSS) aged 8-11.9 years enrolled in the Vascular Function Intervention Trial (ISRCTN74331412/NCT01718054) underwent baseline assessment of endothelium-dependent and -independent vasodilatation. All children were determined clinically well at assessment, hydroxyurea naive, on no long-term medication and not receiving chronic blood transfusions. Blood pressure and vasomotion were assessed after 10 minutes recumbent rest in a temperature controlled room between 08-13:00 hrs. An identical protocol as published in children (Donald & Charakida et al. Eur Heart J; 2010: 31; 1502-10) was used. In brief, brachial arterial endothelium dependent dilatation was assessed by 1 of 3 trained technicians using ultrasound imaging (Ultrasonix SonixTouch with a 12Mz probe & stereotactic holder) to assess flow-mediated dilatation (FMD) in response to reactive hyperaemia induced after release of transient blood pressure cuff occlusion (5 min, 200 mmHg, Hokanson, USA) using an automated air regulator (Logan Research, UK). Automated B-mode image edge detection was used to measure maximum change in arterial diameter (Brachial Tools) expressed as a percentage of resting baseline diameter (FMDmax). Endothelium-independent responses to 2.5µg sub-lingual glyceryl-trinitrate (GTN) were also assessed. All recordings were over-read by an experienced researcher in the UK. Venepuncture for full blood count, clinical chemistry and amino acids was conducted after FMD assessment. Results Patient characteristics are described in Table 1. Mean brachial artery diameter at baseline was 2.61mm (95% CI 2.55 – 2.67mm). Mean FMDmax was 7.70% (95% CI 7.09 – 8.32%). Endothelium-independent vasodilation (GTNmax) was 4.15% (95% CI 3.83 – 4.47%). The FMDmax response was on greater than the GTNmax response (Figure 1). No effect of room or skin temperature on FMDmax or GTNmax was observed. There was a strong inverse association between baseline artery diameter and FMDmax (-3.46, P<0.001) (Figure 2). The time to peak brachial artery diameter in response to hyperaemia was positively skewed (median 55s (IQR: 43-79s)) and was not associated with FMDmax. The only patient characteristic associated with FMDmax was age with a non-significant inverse correlation (-0.52, P=0.06) but was reduced when adjusting for baseline diameter. Baseline heart rate was positively associated with FMDmax and GTNmax (P=0.01 & 0.025). Discussion We have characterised peripheral vascular function in a large cohort of children with SCA. Mean FMDmax was slightly lower than that observed in predominantly Caucasian non-SCA British children of similar age (8.1% [SD3.4]) (Donald & Charakida et al. Eur Heart J 2010: 31; 1502-10), but higher than reported in 21 older French children with SCA (5.6 +/- 0.2) (Montalembert et al. Haematol 2007: 92; 1709-10) which might reflect deterioration of endothelial function with age. There was no apparent association between FMDmax and hemolytic markers or with nutritional status at baseline. Recruitment and assessment of appropriate local non-SCA controls for comparison is planned. Amino acid analyses are ongoing. Disclosures: No relevant conflicts of interest to declare.

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Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01076.2002 ◽

2003 ◽

Vol 285 (5) ◽

pp. H2105-H2110 ◽

Cited By ~ 7

Author(s):

Jian Cui ◽

Rong Zhang ◽

Thad E. Wilson ◽

Sarah Witkowski ◽

Craig G. Crandall ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Heart Rate ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Total Activity ◽

No Synthase ◽

Sympathetic Outflow ◽

Nerve Activity ◽

Head Up Tilt

To test the hypothesis that systemic inhibition of nitric oxide (NO) synthase does not alter the regulation of sympathetic outflow during head-up tilt in humans, in eight healthy subjects NO synthase was blocked by intravenous infusion of NG-monomethyl-l-arginine (l-NMMA). Blood pressure, heart rate, cardiac output, total peripheral resistance (TPR), and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and during 60° head-up tilt. In the supine position, infusion of l-NMMA increased blood pressure, via increased TPR, and inhibited MSNA. However, the increase in MSNA evoked by head-up tilt during l-NMMA infusion (change in burst rate: 24 ± 4 bursts/min; change in total activity: 209 ± 36 U/min) was similar to that during head-up tilt without l-NMMA (change in burst rate: 23 ± 4 bursts/min; change in total activity: 251 ± 52 U/min, n = 6, all P > 0.05). Moreover, changes in TPR and heart rate during head-up tilt were virtually identical between the two conditions. These results suggest that systemic inhibition of NO synthase with l-NMMA does not affect the regulation of sympathetic outflow and vascular resistance during head-up tilt in humans.

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Effect of Cold Stress and the Cold Pressor Test on Blood Pressure and Heart Rate

International Archives of BioMedical and Clinical Research ◽

10.21276/iabcr.2016.2.2.14 ◽

2016 ◽

Vol 2 (2) ◽

Cited By ~ 1

Author(s):

Hajra Banoo

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cold Stress ◽

Cold Pressor Test ◽

Cold Pressor ◽

Pressor Test

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Variability of the haemodynamic responses to laboratory tests employed in assessment of neural cardiovascular regulation in man

Clinical Science ◽

10.1042/cs0690533 ◽

1985 ◽

Vol 69 (5) ◽

pp. 533-540 ◽

Cited By ~ 40

Author(s):

Gianfranco Parati ◽

Guido Pomidossi ◽

Agustin Ramirez ◽

Bruno Cesana ◽

Giuseppe Mancia

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Test Performance ◽

Blood Pressure Response ◽

Cold Pressor Test ◽

Cold Pressor ◽

Cardiovascular Regulation ◽

Pressor Test ◽

Carotid Baroreceptor ◽

Baroreceptor Stimulation

1. In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation. Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses, their reproducibility in any given subject is critical. 2. In 39 subjects with continuous blood pressure (intra-arterial catheter) and heart rate monitoring we measured (i) the blood pressure and heart rate rises during hand-grip and cold-pressor test, (ii) the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine, and (iii) the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber. Each test was carefully standardized and performed at 30 min intervals for a total of six times in each subject. 3. The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied. For the group as a whole the average response variability (coefficient of variation) ranged from 10.2% for the blood pressure response to carotid baroreceptor stimulation to 44.2% for the heart rate response to cold-pressor test. The variability of the responses was not related to basal blood pressure or heart rate, nor to the temporal sequence of the test performance. 4. Thus tests employed for studying neural cardiovascular control in man produce responses whose reproducibility is limited. This phenomenon may make it more difficult to define the response magnitude typical of each subject, as well as its comparison in different conditions and diseases.

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Noise-Enhanced Heart Rate and Sympathetic Nerve Responses to Oscillatory Lower Body Negative Pressure in Humans

Journal of Neurophysiology ◽

10.1152/jn.2001.86.2.559 ◽

2001 ◽

Vol 86 (2) ◽

pp. 559-564 ◽

Cited By ~ 21

Author(s):

Ichiro Hidaka ◽

Shin-Ichi Ando ◽

Hideaki Shigematsu ◽

Koji Sakai ◽

Soko Setoguchi ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Stochastic Resonance ◽

Negative Pressure ◽

Sympathetic Nerve ◽

Carotid Sinus ◽

Lower Body Negative Pressure ◽

Arterial System ◽

Lower Body ◽

Cardiopulmonary Baroreceptors

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as “stochastic resonance.” It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately −10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

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Study of Effect of Shavasana on Handgrip and Cold Pressor Test on Heart Rate and Blood Pressure in Young Adults

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2020/323 ◽

2020 ◽

Vol 9 (18) ◽

pp. 1480-1483

Author(s):

Sandip R Sardessai ◽

Sanjay S Pandarbale

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Young Adults ◽

Cold Pressor Test ◽

Cold Pressor ◽

Pressor Test

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Cardiovascular and norepinephrine responses of men and women to two cold pressor tests

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-006 ◽

1992 ◽

Vol 70 (1) ◽

pp. 36-42 ◽

Cited By ~ 24

Author(s):

J. K. McLean ◽

P. Sathasivam ◽

K. MacNaughton ◽

T. E. Graham

Keyword(s):

Blood Pressure ◽

Gender Differences ◽

Heart Rate ◽

Latin Square ◽

Cold Pressor ◽

Plasma Norepinephrine ◽

Plasma Catecholamine ◽

The Face ◽

Blood Pressure Responses ◽

Venous Plasma

Two types of cold pressor tests were used to study gender differences in cardiovascular and plasma catecholamine responses. Ten male and ten female, young, healthy Caucasian subjects participated. The tests consisted of (1) 5 °C air blown at 3.5–4 m/s onto part of the face for 4 min and (2) the open right hand immersed to the wrist in water at 5 °C for 4 min. Heart rate, blood pressure (BP), and venous plasma norepinephrine were collected before, during, and 5 min after the 4 min of cold exposures. Test order was decided by a Latin square design, and the subjects rested in a quiet room for 30 min between the two tests. All parameters demonstrated significant (p < 0.01) increases from rest during the cold tests. Gender differences were significant (p < 0.01) in diastolic and systolic BP in each test with the males having a greater response, but gender differences were not found in heart rate or norepinephrine concentration. The study demonstrated that gender differences exist in the blood pressure responses to local cold, but that the mechanisms involved do not include a parallel difference in heart rate or venous plasma norepinephrine concentration.Key words: blood pressure, gender differences, stroke volume.

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Acute beetroot juice supplementation on sympathetic nerve activity: a randomized, double-blind, placebo-controlled proof-of-concept study

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00163.2017 ◽

2017 ◽

Vol 313 (1) ◽

pp. H59-H65 ◽

Cited By ~ 28

Author(s):

Karambir Notay ◽

Anthony V. Incognito ◽

Philip J. Millar

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Sympathetic Outflow ◽

Beetroot Juice ◽

Proof Of Concept ◽

Burst Frequency ◽

Double Blind ◽

Dietary Nitrate ◽

Nitrate Supplementation ◽

Central Sympathetic Outflow

Acute dietary nitrate ([Formula: see text]) supplementation reduces resting blood pressure in healthy normotensives. This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation, although nitric oxide also tonically inhibits central sympathetic outflow. We hypothesized that acute dietary [Formula: see text] supplementation using beetroot (BR) juice would reduce blood pressure and muscle sympathetic nerve activity (MSNA) at rest and during exercise. Fourteen participants (7 men and 7 women, age: 25 ± 10 yr) underwent blood pressure and MSNA measurements before and after (165–180 min) ingestion of 70ml high-[Formula: see text] (~6.4 mmol [Formula: see text]) BR or [Formula: see text]-depleted BR placebo (PL; ~0.0055 mmol [Formula: see text]) in a double-blind, randomized, crossover design. Blood pressure and MSNA were also collected during 2 min of static handgrip (30% maximal voluntary contraction). The changes in resting MSNA burst frequency (−3 ± 5 vs. 3 ± 4 bursts/min, P = 0.001) and burst incidence (−4 ± 7 vs. 4 ± 5 bursts/100 heart beats, P = 0.002) were lower after BR versus PL, whereas systolic blood pressure (−1 ± 5 vs. 2 ± 5 mmHg, P = 0.30) and diastolic blood pressure (4 ± 5 vs. 5 ± 7 mmHg, P = 0.68) as well as spontaneous arterial sympathetic baroreflex sensitivity ( P = 0.95) were not different. During static handgrip, the change in MSNA burst incidence (1 ± 8 vs. 8 ± 9 bursts/100 heart beats, P = 0.04) was lower after BR versus PL, whereas MSNA burst frequency (6 ± 6 vs. 11 ± 10 bursts/min, P = 0.11) as well as systolic blood pressure (11 ± 7 vs. 12 ± 8 mmHg, P = 0.94) and diastolic blood pressure (11 ± 4 vs. 11 ± 4 mmHg, P = 0.60) were not different. Collectively, these data provide proof of principle that acute BR supplementation can decrease central sympathetic outflow at rest and during exercise. Dietary [Formula: see text] supplementation may represent a novel intervention to target exaggerated sympathetic outflow in clinical populations. NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation. Here, we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population. These results have applications for targeting central sympathetic overactivation in disease.

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