Blood Pressure Regulation by the Carotid Sinus Nerve: Clinical Implications for Carotid Body Neuromodulation

Chronic carotid sinus nerve (CSN) electrical modulation through kilohertz frequency alternating current improves metabolic control in rat models of type 2 diabetes, underpinning the potential of bioelectronic modulation of the CSN as a therapeutic modality for metabolic diseases in humans. The CSN carries sensory information from the carotid bodies, peripheral chemoreceptor organs that respond to changes in blood biochemical modifications such as hypoxia, hypercapnia, acidosis, and hyperinsulinemia. In addition, the CSN also delivers information from carotid sinus baroreceptors—mechanoreceptor sensory neurons directly involved in the control of blood pressure—to the central nervous system. The interaction between these powerful reflex systems—chemoreflex and baroreflex—whose sensory receptors are in anatomical proximity, may be regarded as a drawback to the development of selective bioelectronic tools to modulate the CSN. Herein we aimed to disclose CSN influence on cardiovascular regulation, particularly under hypoxic conditions, and we tested the hypothesis that neuromodulation of the CSN, either by electrical stimuli or surgical means, does not significantly impact blood pressure. Experiments were performed in Wistar rats aged 10–12 weeks. No significant effects of acute hypoxia were observed in systolic or diastolic blood pressure or heart rate although there was a significant activation of the cardiac sympathetic nervous system. We conclude that chemoreceptor activation by hypoxia leads to an expected increase in sympathetic activity accompanied by compensatory regional mechanisms that assure blood flow to regional beds and maintenance of hemodynamic homeostasis. Upon surgical denervation or electrical block of the CSN, the increase in cardiac sympathetic nervous system activity in response to hypoxia was lost, and there were no significant changes in blood pressure in comparison to control animals. We conclude that the responses to hypoxia and vasomotor control short-term regulation of blood pressure are dissociated in terms of hypoxic response but integrated to generate an effector response to a given change in arterial pressure.

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FMRF-amide and L-Arg-L-Phe increase blood pressure and heart rate in the anaesthetised rat by central stimulation of the sympathetic nervous system

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(05)81237-9 ◽

1991 ◽

Vol 175 (1) ◽

pp. 318-324 ◽

Cited By ~ 24

Author(s):

Christoph Thiemermann ◽

Saad Al-Damluji ◽

Markus Hecker ◽

John R. Vane

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Nervous System ◽

Sympathetic Nervous System ◽

Increase Blood Pressure ◽

Sympathetic Nervous ◽

Fmrf Amide ◽

Anaesthetised Rat ◽

Central Stimulation ◽

Stimulation Of

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Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo

Clinical Science ◽

10.1042/cs20060365 ◽

2007 ◽

Vol 113 (1) ◽

pp. 33-40 ◽

Cited By ~ 7

Author(s):

Niels P. Riksen ◽

Marlies Bosselaar ◽

Stephan J.L. Bakker ◽

Robert J. Heine ◽

Gerard A. Rongen ◽

...

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Adenosine Receptor ◽

Pulse Wave ◽

Adenosine Receptor Antagonist ◽

Sympathetic Nervous ◽

Control Infusion

Plasma NEFA (non-esterified fatty acid) concentrations are elevated in patients with obesity. In the present study we first aimed to provide an integral haemodynamic profile of elevated plasma NEFAs by the simultaneous assessment of blood pressure, pulse wave velocity, FBF (forearm blood flow) and sympathetic nervous system activity during acute elevation of NEFAs. Secondly, we hypothesized that NEFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized cross-over trial in healthy subjects, Intralipid® was infused for 2 h to elevate plasma NEFAs. Glycerol was administered as the Control infusion. We assessed blood pressure, pulse wave velocity, FBF (using venous occlusion plethysmography) and sympathetic nervous system activity by measurement of noradrenaline and adrenaline. During the last 15 min of Intralipid®/Control infusion, the adenosine receptor antagonist caffeine (90 μg·min−1·dl−1) was administered into the brachial artery of the non-dominant arm. Compared with Control infusion, Intralipid® increased pulse wave velocity, SBP (systolic blood pressure) and pulse pressure, as well as FBF (from 1.8±0.2 to 2.7±0.6 and from 2.3±0.2 to 2.7±0.6 ml·min−1·dl−1 for Intralipid® compared with Control infusion; P<0.05, n=9). Although in a positive control study caffeine attenuated adenosine-induced forearm vasodilation (P<0.01, n=6), caffeine had no effect on Intralipid®-induced vasodilation (P=0.5). In conclusion, elevation of plasma NEFA levels increased pulse wave velocity, SBP and pulse pressure. FBF was also increased, either by baroreflex-mediated inhibition of the sympathetic nervous system or by a direct vasodilating effect of NEFAs. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, this response is not mediated by adenosine receptor stimulation.

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Role of Sympathetic Nervous System in Cyclosporine-Induced Rise in Blood Pressure

Hypertension ◽

10.1161/01.hyp.34.1.102 ◽

1999 ◽

Vol 34 (1) ◽

pp. 102-106 ◽

Cited By ~ 12

Author(s):

Mario J. Carvalho ◽

Anton H. van den Meiracker ◽

Frans Boomsma ◽

Joao Freitas ◽

Arie J. Man in ‘t Veld ◽

...

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Sympathetic Nervous

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Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.262.6.e763 ◽

1992 ◽

Vol 262 (6) ◽

pp. E763-E778 ◽

Cited By ~ 136

Author(s):

I. A. Reid

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Blood Pressure Control ◽

Cardiovascular Responses ◽

Pressure Control ◽

Ang Ii ◽

Arterial Blood ◽

Baroreceptor Reflexes ◽

Sympathetic Nervous

The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system.

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Abstract 291: Antihypertensive Effect Of Bia 5-1058 a New Selective Peripheral Dopamine β-hydroxylase Inhibitor

Hypertension ◽

10.1161/hyp.60.suppl_1.a291 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Bruno Igreja ◽

Nuno M Pires ◽

Lyndon C Wright ◽

Patrío Soares-da-Silva

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Receptor Antagonist ◽

Antihypertensive Effect ◽

Antihypertensive Drugs ◽

Radio Telemetry ◽

Sympathetic Nerves ◽

Maximum Reduction ◽

Sympathetic Nervous

The sympathetic nervous system can alter blood pressure by modulation of cardiac output, peripheral vascular resistance and renal function. One strategy for controlling sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH; EC 1.14.17.1 ), the enzyme that catalyses the conversion of dopamine (DA) to NE in sympathetic nerves. BIA 5-1058 is a reversible DβH inhibitor that decreases NE levels in peripheral sympathetically innervated tissues slowing down sympathetic nervous system drive, without effect in brain tissues. In freely moving SHR implanted with radio-telemetry transmitters single administration of BIA 5-1058 showed a dose (3, 30 and 100 mg/Kg) and time dependent effect on blood pressure with no significant effect on heart rate (HR) and total activity monitored over a 96-hour period. The maximum reduction on systolic blood pressure (SBP) was -10.8, -21.1 and -35.2 mmHg for 3, 30 and 100 mg/Kg, respectively and the maximum reduction on diastolic blood pressure (DBP) was -9.9, -18.4 and -24.8 mmHg for 3, 30 and 100 mg/Kg, respectively. The antihypertensive effect of BIA 5-1058 (30 mg/Kg) was further evaluated in combination with efficacious doses of well-known antihypertensive drugs, like the ACE inhibitor captopril, the AT1 receptor antagonist losartan, the diuretic hydrochlorothiazide, beta-blocker metoprolol, the alpha-1 receptor antagonist prazosin, and the calcium channel blocker diltiazem. All drugs were administered orally (single dose) in a cross-over design and the effect was monitored for 72 hours. The combination of BIA 5-1058 with any of the tested antihypertensive drugs caused a stronger and prolonged blood pressure decrease than any of the compounds alone.In conclusion, peripheral DβH inhibitors can be used, alone or in combination with others antihypertensive drugs, to reduce blood pressure.

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Blood pressure control and the peripheral sympathetic nervous system

Mild Hypertension ◽

10.1007/978-3-642-85334-0_3 ◽

1984 ◽

pp. 24-33

Author(s):

C. J. Mathias

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Blood Pressure Control ◽

Pressure Control ◽

Sympathetic Nervous ◽

Peripheral Sympathetic Nervous System

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The sympathetic muscle metaboreflex is not different in the third trimester in normotensive pregnant women.

Journal of Applied Physiology ◽

10.1152/japplphysiol.00728.2020 ◽

2020 ◽

Author(s):

Rachel J. Skow ◽

Andrew R. Steele ◽

Graham M. Fraser ◽

Margie H. Davenport ◽

Craig D. Steinback

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Pregnant Women ◽

Isometric Handgrip ◽

Third Trimester ◽

Muscle Metaboreflex ◽

The Third ◽

Arterial Blood ◽

Sympathetic Nervous

Isometric handgrip (IHG) is used to assess sympathetic nervous system responses to exercise and may be useful at predicting hypertension in both pregnant and non-pregnant populations. We have previously observed altered sympathetic nervous system control of blood pressure in late pregnancy. Therefore, we measured muscle sympathetic nerve activity (MSNA) and blood pressure during muscle metaboreflex activation (IHG) in normotensive pregnant women in the third trimester compared to healthy non-pregnant women. Nineteen pregnant (32±3wks gestation) and fourteen non-pregnant women were matched for age, non/pre-pregnant BMI, and parity. MSNA (microneurography), heart rate (ECG), and arterial blood pressure (Finometer) were continuously recorded during ten minutes of rest, and then during two-minutes of IHG at 30% of maximal voluntary contraction, and two-minutes of post-exercise circulatory occlusion (PECO). Baseline SNA was elevated in pregnant (41±11 bursts/min) compared to non-pregnant women (27 ± 9 bursts/minute; p=0.005); however, the sympathetic baroreflex gain and neurovascular transduction were not different between groups (p=0.62 and p=0.32, respectively). During IHG and PECO there was no significant differences in the pressor response (∆MAP) during IHG and PECO was not different between groups (p=0.25, main effect of group) nor the sympathetic response (interaction effect: p=0.16, 0.25, and 0.27 for burst frequency, burst incidence, and total SNA respectively). These data suggest that pregnant women who have maintained sympathetic baroreflex and neurovascular transduction also have similar sympathetic and pressor responses during exercise.

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Interaction of the sympathetic nervous system with vasopressin and renin in the maintenance of blood pressure.

Hypertension ◽

10.1161/01.hyp.4.3.400 ◽

1982 ◽

Vol 4 (3) ◽

pp. 400-405 ◽

Cited By ~ 69

Author(s):

H Gavras ◽

P Hatzinikolaou ◽

W G North ◽

M Bresnahan ◽

I Gavras

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Sympathetic Nervous

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Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00411.2014 ◽

2015 ◽

Vol 308 (8) ◽

pp. R708-R713 ◽

Cited By ~ 22

Author(s):

Rodrigo Maranon ◽

Roberta Lima ◽

Frank T. Spradley ◽

Jussara M. do Carmo ◽

Howei Zhang ◽

...

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Female Rats ◽

Elevated Blood Pressure ◽

Renal Nerves ◽

Female Rat ◽

Elevated Blood ◽

Melanocortin 4 Receptor ◽

Sympathetic Nervous

Women with polycystic ovary syndrome (PCOS) have hyperandrogenemia and increased prevalence of risk factors for cardiovascular disease, including elevated blood pressure. We recently characterized a hyperandrogenemic female rat (HAF) model of PCOS [chronic dihydrotestosterone (DHT) beginning at 4 wk of age] that exhibits similar characteristics as women with PCOS. In the present studies we tested the hypotheses that the elevated blood pressure in HAF rats is mediated in part by sympathetic activation, renal nerves, and melanocortin-4 receptor (MC4R) activation. Adrenergic blockade with terazosin and propranolol or renal denervation reduced mean arterial pressure (MAP by telemetry) in HAF rats but not controls. Hypothalamic MC4R expression was higher in HAF rats than controls, and central nervous system MC4R antagonism with SHU-9119 (1 nmol/h icv) reduced MAP in HAF rats. Taking a genetic approach, MC4R null and wild-type (WT) female rats were treated with DHT or placebo from 5 to 16 wk of age. MC4R null rats were obese and had higher MAP than WT control rats, and while DHT increased MAP in WT controls, DHT failed to further increase MAP in MC4R null rats. These data suggest that increases in MAP with chronic hyperandrogenemia in female rats are due, in part, to activation of the sympathetic nervous system, renal nerves, and MC4R and may provide novel insights into the mechanisms responsible for hypertension in women with hyperandrogenemia such as PCOS.

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