Postganglionic Sympathetic Nerve Activity Research Articles

503 Stimulation of the Paraventricular Nucleus Activates Brown Adipose Tissue via Local GABA Release: A Novel Target for the Treatment of Obesity

INTRODUCTION: Sympathetic activation of brown adipose tissue (BAT) has shown significant promise in preclinical studies to elicit long term weight loss and reversal of type 2 diabetes however it is inhibited in obese individuals. METHODS: Rats were anesthetized and monitored for body temperature, BAT temperature, expired CO2, mean arterial pressure, and heart rate. Postganglionic BAT sympathetic nerve activity (SNA) was recorded from the interscapular BAT pad. Stimulating electrode and micropipette were placed steroeotactically in the PVN. Stimulation pulses at an intensity of 100 µA at 100 Hz for 5 minutes were delivered. Changes in BAT SNA and physiology were compared with and without stereotactically injected 500 µM bicuculline, a GABAA receptor antagonist. RESULTS: Stimulation of the PVN increased BAT SNA compared to no stimulation (411.7 ± 75.8% baseline vs 98.18 ± 1.4% baseline n = 5; P < 0.05) along with BAT temperature (35.8 ± 0.8°C vs 34.2 ± 0.7°C, n = 5, P < 0.001), expired CO2 (4.7 ± 0.6% vs 4.2 ± 0.5%, n = 5, P < 0.05) indicating increased metabolic rate. There was no change in blood pressure, body temperature, or paw temperature suggesting no change in sympathetic tone. Heart rate increased (476 ± 21 bpm vs 429 ± 23 bpm, n = 5, P < 0.01) consistent with increased metabolic demand. Microinjection of 500 µM bicuculline into the PVN prevented stimulated activation of BAT SNA. CONCLUSIONS: Stimulation of the PVN increases BAT activation and basal metabolic activity in the absence of cold-stimulus with minimal off-target effects on systemic sympathetic tone and may be a viable therapeutic target for stimulation of BAT activity to treat obesity and type 2 diabetes.

Maintenance of contractile force of the hind limb muscles by the somato-lumbar sympathetic reflexes

This study aimed to clarify whether the reflex excitation of muscle sympathetic nerves induced by contractions of the skeletal muscles modulates their contractility. In anesthetized rats, isometric tetanic contractions of the triceps surae muscles were induced by electrical stimulation of the intact tibial nerve before and after transection of the lumbar sympathetic trunk (LST), spinal cord, or dorsal roots. The amplitude of the tetanic force (TF) was reduced by approximately 10% at 20 min after transection of the LST, spinal cord, or dorsal roots. The recorded postganglionic sympathetic nerve activity from the lumbar gray ramus revealed that both spinal and supraspinal reflexes were induced in response to the contractions. Repetitive electrical stimulation of the cut peripheral end of the LST increased the TF amplitude. Our results indicated that the spinal and supraspinal somato-sympathetic nerve reflexes induced by contractions of the skeletal muscles contribute to the maintenance of their own contractile force.

Activation of Bradykinin‐Sensitive Pericardial Afferents Increases Splanchnic Nerve Activity

Sympathetic drive plays a key role in control of cardiovascular function. The heart performs an important sensory function via a variety of cardiac receptors that modulate sympathetic drive. Bradykinin‐sensitive sympathetic afferent nerves from the heart can trigger marked increases in efferent sympathetic nerve activity to some cardiovascular targets such as the kidney. We reported previously that pericardial injection of bradykinin increased venous tone and cardiac output. The splanchnic vascular compartment plays an important role in control of venous return and cardiac output. This work tested the hypothesis that activation of bradykinin‐sensitive pericardial afferents increases postganglionic splanchnic sympathetic nerve activity.Sprague Dawley rats were anesthetized with a cocktail of alpha chloralose (80 mg/kg) and urethane (800 mg/kg). Catheters were placed in the femoral artery and vein to record arterial pressure (MAP) and heart rate (HR). A PE10 catheter was placed in the pericardial space for the injection of bradykinin (BK), an agent known to stimulate cardiac sympathetic afferents. The chest was closed and the rat allowed to breathe spontaneously. The splanchnic sympathetic nerve was isolated via a dorsal approach and placed on recording electrodes. After stabilization, the blood pressure, heart rate, and integrated splanchnic nerve activity (SPLNA) responses to pericardial injection of BK or vehicle were recorded. Responses were also recorded for intravenous injection of dimethylphenylpiperazinium (DMPP 150 ug/kg), a ganglionic stimulant, and a ganglion blocker (hexamethonium 20 mg/kg).Pericardial injection of saline vehicle had little effect (MAP: 0.1±0.4 mm Hg; HR: 1.2±1.4 bpm; SPLNA 1±2%). In contrast, intravenous injection of a ganglionic stimulant, DMPP, increased MAP (23±1 mm Hg) and SPLNA (95±46%). Pericardial injection of BK (10 ug/kg) increased MAP (21±3 mm Hg), HR (28±7 bpm) and SPLNA (93±37%). Ganglionic blockade with hexamethonium reduced SPLNA (−75±6%) and abolished the responses to pericardial injection of BK (MAP: −1±3 mm Hg; HR: −2±1 bpm; SPLNA: 7±30 %).We interpret these data to indicate that activation of bradykinin‐sensitive pericardial afferents increases postganglionic splanchnic sympathetic nerve activity. This finding is consistent with the view that activation of the cardiac sympathetic afferent reflex elicits a venoconstrictor response to increase venous return from the splanchnic vascular compartment.Support or Funding InformationSupported by NIH R01 HL136741‐03 (DM), R01 DK114663‐1 (HZ), and the Basic Biomedical Sciences program of the Sanford School of Medicine, University of South Dakota.

Epidural Spinal Cord Stimulation Acutely Reduces Efferent Postganglionic Sympathetic Nerve Activity in Humans

Evidence in clinical and animal studies demonstrates that epidural spinal cord stimulation (SCS) mimics the effects of sympathetic block or sympathectomy and increases peripheral blood flow. However, the extent to which SCS lowers sympathetic nerve activity in humans remains unclear because no studies have directly assessed muscle sympathetic nerve activity (MSNA) responses to SCS. We tested the hypothesis that acute SCS (60 min) at the lower thoracic spine would 1) lead to reduced MSNA in the peroneal nerve, and 2) increase blood flow in the legs, but not the arms. Twelve patients (54 ± 3 yrs, 5 men/7 women) that previously underwent surgical implantation of a SCS device for management of neuropathic pain were studied. Following 48 hours of no SCS, femoral and brachial artery blood flow was assessed using Doppler ultrasound at baseline and at 15, 30, 45, 60 min of SCS, and 15 min post SCS. MSNA was assessed using microneurography under the same conditions during a second visit (n=5). Femoral artery blood flow was significantly increased throughout SCS and 15 min post SCS (15 min: 26 ± 1%, 30 min: 32 ± 14%, 45 min: 30 ± 13%, 60 min: 26 ± 13%, 15 min post SCS: 40 ± 14% ml/min, P=0.02), but no change in brachial artery blood flow was observed (15 min: 4 ± 6%, 30 min: 5 ± 8%, 45 min: 5 ± 7%, 60 min: 7 ± 7% ml/min, 15 min post SCS: 6 ± 11% ml/min, P=0.86). MSNA was progressively reduced during SCS, reaching significance at 45 and 60 min, and returned toward baseline following SCS (15 min: −1 ± 6%, 30 min: −13 ± 4%, 45 min: −17 ± 6%, 60 min: −21 ± 7%, 15 min post SCS: −4 ± 5% bursts/100heartbeats, P=0.01). Similar results were observed for MSNA total activity (AU/min) (P<0.042). During measures of MSNA, self‐reported neuropathic pain was low at baseline and not significantly changed by SCS (scale 0–10; BL: 2.8 ± 0.8, 15 min: 1.7 ± 0.9, 30 min: 1.5 ± 1, 45 min: 1.7 ± 1, 60 min: 1.5 ± 1, P=0.07), suggesting that reductions in MSNA were SCS‐mediated and not primarily a result of pain relief. These preliminary results demonstrate proof of principle that acute lower thoracic SCS significantly reduces peroneal MSNA in humans.Support or Funding InformationAHA 17POST33440101, T32 HL07121, NHLBI (P01HL014388), U54 TR001356 and AHA (13DG143400012)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans.

As a primary component of homeostasis, the sympathetic nervous system enables rapid adjustments to stress through its ability to communicate messages among organs and cause targeted and graded end organ responses. Key in this communication model is the pattern of neural signals emanating from the central to peripheral components of the sympathetic nervous system. But what is the communication strategy employed in peripheral sympathetic nerve activity (SNA)? Can we develop and interpret the system of coding in SNA that improves our understanding of the neural control of the circulation? In 1968, Hagbarth and Vallbo (Hagbarth KE, Vallbo AB. Acta Physiol Scand 74: 96-108, 1968) reported the first use of microneurographic methods to record sympathetic discharges in peripheral nerves of conscious humans, allowing quantification of SNA at rest and sympathetic responsiveness to physiological stressors in health and disease. This technique also has enabled a growing investigation into the coding patterns within, and cardiovascular outcomes associated with, postganglionic SNA. This review outlines how results obtained by microneurographic means have improved our understanding of SNA outflow patterns at the action potential level, focusing on SNA directed toward skeletal muscle in conscious humans.

PP.LB02.15] RENAL DENERVATION NORMALIZES SYMPATHETIC VASOMOTOR ACTIVITY AND PRODUCES DIFFERENTIAL EFFECTS ON THE ARTERIAL BARORECEPTOR FUNCTION IN THE GOLDBLATT RENOVASCULAR HYPERTENSION

Objective: Sympathetic nerve activity is increased in renovascular hypertension. Renal denervation has shown promise in the treatment of patients with resistant hypertension to drug therapy, although the mechanisms underlying reduction in blood pressure remains uncertain. The aim of this study was to evaluate the effects of unilateral renal denervation (H+DnX) on efferent post-ganglionic sympathetic nerve activity to renal (rSNA) and lumbar (lSNA) sympathetic nerves in Goldblatt hypertensive rats (2K1C). Design and method: The baroreceptor sensitivity to rSNA, lSNA, heart rate (HR) and the cardiovascular autonomic function (by power spectral density analysis) were evaluated ten days after renal denervation. Denervation of clipped kidney (DnX – all visible bundles nerves were dissected – 10% phenol) was performed 5 weeks after clipping (gap width 0.2 mm). The rSNA and barorreceptor reflex control to rSNA was performed in the innervated contralateral kidney. Results: Ten days after DnX, blood pressure (BP) was significantly reduced (16%) in the 2K1C rats compared to 2K1C undenervated (H). DnX normalized rSNA (CT: 110 ± 8, n = 14; 2K1C:150 ± 8, n = 12; 2K1C DnX:89 ± 7, pps n = 8) and lSNA (CT: 137 ± 8, n = 8; 2K1C: 202 ± 7, n = 11; 2K1C DnX:131 ± 7, pps n = 8) in the 2K1C rats. DnX significantly improved the baroreceptor function for rSNA (CT: −2.3 ± 0.2, n = 11; 2K1C: −0.7 ± 0.1, n = 8; 2K1C DnX: −1.5 ± 0.2, pps/mmHg n = 5) and tachycardic response (CT: −3.9 ± 0.5, n = 7; 2K1C: −1.9 ± 0.1, n = 8; 2K1C DnX: −3.3 ± 0.4, bpm/mmHg n = 8), but not for lSNA in 2K1C rats. Furthermore, DnX significantly increased the high frequency (HF) component (CT: 1.4 ± 1, n = 10; 2K1C: 3.4 ± 2 n = 9; 2K1C DnX: 7.6 ± 3, ms2 n = 9) but not the very low frequency (VLF) and low frequency (LF) components (VLF = CT: 2.7 ± 1, n = 10; 2K1C: 13 ± 7, n = 9; 2K1C DnX: 9 ± 5, ms2 n = 8 / LF = CT: 2 ± 0.6, n = 9; 2K1C: 5 ± 3, n = 11; 2K1C DnX: 6 ± 4, ms2 n = 9) which remained elevated in the 2K1C rats. Conclusions: The results show that renal denervation normalized sympathetic vasomotor activity and increased the HF component of spectral analysis accompanied by a non uniform improvement in the arterial baroreceptor function. Whether the baroreceptor function sensitivity improvement induced by DnX is a cause or a consequence of BP reduction remains to be determined. Supported by FAPESP and CAPES.

Neural Control of Vascular Function in Skeletal Muscle.

The sympathetic nervous system represents a fundamental homeostatic system that exerts considerable control over blood pressure and the distribution of blood flow. This process has been referred to as neurovascular control. Overall, the concept of neurovascular control includes the following elements: efferent postganglionic sympathetic nerve activity, neurotransmitter release, and the end organ response. Each of these elements reflects multiple levels of control that, in turn, affect complex patterns of change in vascular contractile state. Primarily, this review discusses several of these control layers that combine to produce the integrative physiology of reflex vascular control observed in skeletal muscle. Beginning with three reflexes that provide somewhat dissimilar vascular patterns of response despite similar changes in efferent sympathetic nerve activity, namely, the baroreflex, chemoreflex, and muscle metaboreflex, the article discusses the anatomical and physiological bases of postganglionic sympathetic discharge patterns and recruitment, neurotransmitter release and management, and details of regional variations of receptor density and responses within the microvascular bed. Challenges are addressed regarding the fundamentals of measurement and how conclusions from one response or vascular segment should not be used as an indication of neurovascular control as a generalized physiological dogma. Whereas the bulk of the article focuses on the vasoconstrictor function of sympathetic neurovascular integration, attention is also given to the issues of sympathetic vasodilation as well as the impact of chronic changes in sympathetic activation and innervation on vascular health. © 2016 American Physiological Society.

5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation

Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure.

Dysautonomic responses during percutaneous carotid intervention: principles of physiology and management.

Percutaneous carotid artery stenting (CAS) has emerged as a less invasive alternative to carotid endarterectomy for the treatment of carotid atherosclerotic disease. The main risk of CAS is the occurrence of neuro-vascular complications; however, carotid artery stenting-related dysautonomia (CAS-D) (hypertension, hypotension, and bradycardia) is the most frequently reported problem occurring in the periprocedural period. Alterations in autonomic homeostasis result from baroreceptor stimulation, which occurs particularly at the time of balloon inflation in the region of the carotid sinus. The response can be profound enough to induce asystole or even complete cessation of postganglionic sympathetic nerve activity. Frequency and factors predisposing a patient to CAS-D have been investigated in several studies; however, there are significant discrepancies in results among reports. Lack of consistent findings may arise from using different methods and definitions, as well as other factors discussed in detail in this review. Furthermore, a correlation of CAS-D with short and long-term outcomes has been investigated only in small and mostly retrospective studies, explaining why its prognostic significance remains uncertain. In this manuscript, we have focused on risk factors, pathophysiology and management of periprocedural autonomic dysfunction. As there is no standardized approach to the treatment of CAS-D, we present an algorithm for the periprocedural management of patients undergoing CAS. The proposed algorithm was developed based on our procedural experience as well as data from the available literature. The Yale Algorithm was successfully implemented at our institution and we are currently collecting data for short- and long-term safety. © 2014 Wiley Periodicals, Inc.

Sympathetic neural tone: large and in charge throughout pregnancy

Sympathetic neural tone: large and in charge <i>throughout</i> pregnancy

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

P2.18 Action potential content in human postganglionic sympathetic nerve activity during severe reflex mediated autonomic arousal

P2.18 Action potential content in human postganglionic sympathetic nerve activity during severe reflex mediated autonomic arousal

Effect of depth of anaesthesia and postganglionic sympathetic blockade on reflex heart rate control in rodents during lower body negative pressure

We tested the hypothesis that depth of anaesthesia affects heart rate (HR) control during orthostatic stress in rodents. Urethane (UR) and a‐chlorolose (a‐CL) were injected IP to reach either a Light (n=4; 25mg UR/100g rat mass, 3.5mg a‐CL/100g rat mass) or Deep (n=3; 40mg UR/100g rat mass, 4.0mg a‐CL/100g rat mass; IV top‐ups as needed) plane of anaesthesia, verified by the respective presence or absence of ear twitch, palpebral and pedal reflexes. Orthostatic stress was achieved with lower body negative pressure (LBNP), adapted for a rat model. Cardiac output (Q; transonic flow‐meter at descending aorta) and HR (ECG) were measured during graded bouts of LBNP between ‐1 and ‐10 mmHg, ordered randomly. At each anaesthetic depth LBNP was repeated with saline or hexamethonium (HEX; 25mg/kg IV) to block postganglionic sympathetic nerve activity. The reduction in Q during LBNP (main effect, P&lt;0.05) was not affected by anaesthetic depth or HEX. HR increased with LBNP when suction exceeded ‐4 mmHg (main effect, P&lt;0.05). Focusing on ‐10 mmHg, the HR increase was not different between Light (24±10 bpm) and Deep (24±7 bpm) planes, but was attenuated with HEX (4±1 and 5±5 bpm, P&lt;0.001 vs. Light and Deep, respectively). These preliminary results suggest that the majority of the HR response to LBNP in rodents is mediated by postganglionic sympathetic outflow and is not affected by depth of anaesthesia.Support provided by CIHR and NSERC.

Activation of 5-HT1A receptors in rostral medullary raphé inhibits cutaneous vasoconstriction elicited by cold exposure in rabbits

In both conscious and anesthetized rabbits, we determined whether microinjection of a 5-hydroxytryptamine (5-HT) 1A receptor agonist 8-hydroxy-2-(di- n-propylaminio) tetralin (8-OH-DPAT) into the medullary raphé/parapyramidal region inhibits thermoregulatory vasoconstriction and whether microinjection of a 5-HT1A receptor antagonist ( N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)- N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (WAY-100635) into the raphé reverses the cutaneous vasomotor changes induced by intravenous administration of 8-OH-DPAT. In conscious rabbits with measuring ear pinna blood flow, after microinjection of 8-OH-DPAT (3–5 nmol in 300–500 nl) into the raphé, transferring the animal from a warm cage (25–28 °C) to a cold cage (5–10 °C) did not reduce the ear pinna flow (from 57 ± 7 cm/s to 59 ± 3 cm/s, P > 0.05, n = 5), unlike Ringer-treated animals. Microinjection of WAY-100635 (5 nmol in 500 nl) into the raphé reversed ear pinna flow changes induced by intravenous administration of 8-OH-DPAT (0.1 mg/kg, i.v.). In anesthetized rabbits with measuring postganglionic ear pinna sympathetic nerve activity, microinjection of 8-OH-DPAT (1–2 nmol in 100–200 nl) into the raphé reduced resting ear pinna sympathetic nerve activity to 14 ± 4% of pre-injection level ( P < 0.01, n = 12) and attenuated increases in ear pinna sympathetic nerve activity normally elicited by cooling the animal's trunk. WAY-100635 (2 nmol into 200 nl) into the raphé reversed inhibition of ear pinna sympathetic nerve activity elicited by 8-OH-DPAT (0.1 mg/kg, i.v.). The activation of 5-HT1A receptors expressed on the medullary raphé neurons results in reversal of cold-elicited cutaneous vasoconstriction possibly through inhibition of sympathetic premotor neurons that innervate sympathetic preganglionic neurons controlling cutaneous vasomotion.

5-Hydroxytryptamine 1A receptors inhibit cold-induced sympathetically mediated cutaneous vasoconstriction in rabbits.

5-HT1A receptor agonists lower body temperature. We have investigated whether activation of 5-HT1A receptors inhibits cutaneous sympathetic discharge so that dilatation of the cutaneous vascular bed lowers body temperature by increasing heat transfer to the environment. We measured ear pinna blood flow in conscious rabbits (with chronically implanted Doppler ultrasound flow probes), and postganglionic sympathetic vasomotor nerve activity in anaesthetized rabbits. Recordings from conscious rabbits were made in a cage at 26 degrees C and the rabbit was then transferred to a cage at 10 degrees C. The ear pinna Doppler signal fell from 56 +/- 4 cm s-1 in the 26 degrees C cage to 4 +/- 1 cm s-1 (P < 0.0001, n = 24) after 30 min in the 10 degrees C cage, and body temperature increased from 38.8 +/- 0.2 to 39.0 +/- 0.2 degrees C (P < 0.01, n = 24). The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg kg-1 I.V.) reversed the cold-induced fall in ear pinna blood flow (Doppler signal increased from 5 +/- 1 to 55 +/- 8 cm s-1, P < 0.001, n = 7) within 5 min when administered 30 min after transfer to the 10 degrees C cage, and prevented the fall in ear pinna blood flow when administered before the rabbit was transferred to the 10 degrees C cage. Body temperature decreased after administration of 8-OH-DPAT. These changes were abolished by the specific 5-HT1A antagonist WAY-100635 (0.1 mg kg-1 I.V.). In anaesthetized rabbits, 8-OH-DPAT (0.1 mg kg-1 I.V.) reduced resting postganglionic cutaneous sympathetic vasomotor discharge, and prevented the increase normally elicited by cooling the trunk. Our experiments constitute the first demonstration that activation of 5-HT1A receptors powerfully inhibits cold-induced increases in cutaneous sympathetic vasomotor discharge, thereby dilating the cutaneous vascular bed and increasing transfer of heat to the environment.

Complete vasomotor collapse: an unusual manifestation of the carotid sinus reflex.

Complete vasomotor collapse: an unusual manifestation of the carotid sinus reflex.

Saccular and utricular influences on sympathetic nerve activities in cats.

We studied the effects of stimulation of the utricular and saccular nerves on sympathetic nerve activity in decerebrated cats. Bipolar electrodes were fixed in place on the utricular and/or saccular nerve under visual observation; the other branches of the vestibular nerve were transected. Baroreceptors and vagus nerves were inactivated bilaterally so that inputs from baroreceptors and other visceral receptors did not influence the sympathetic nerve outflow. Postganglionic sympathetic nerve activity was recorded from the renal branch of the sympathetic nerve, which is known to be more sensitive to vestibular stimuli than other types of sympathetic fibers. With stimulation of either the saccular or utricular nerve at low stimulus intensity, a prominent inhibition followed by a rebound excitation was evoked on spontaneous renal nerve discharges. The latency of the inhibition ranged from 65 to 130 ms, and the duration of inhibitory responses was about 90-150 ms. An increase in stimulus intensity in both the saccular and utricular nerves induced inhibitory effects preceded by short-term excitation. The latency of this excitation, which was superimposed on the initial phase of the inhibitory responses, ranged from 55 to 90 ms.

Role of nitric oxide in the regulation of cardiovascular autonomic control

Alteration in function of the cardiac autonomic nervous system has proved to be a powerful predictor of cardiac death or serious arrhythmia in patients with cardiac disease, yet little is known about the mechanisms by which this system is regulated. Recent evidence suggests that the gaseous molecule nitric oxide (NO) may act as an important mediator in this pathway. Histochemical staining techniques have identified neuronal populations that contain NO synthase within medullary cardio-regulatory sites and their peripheral autonomic pathways. Drugs that modulate the NO pathway (administered both systemically and into the central nervous system) cause changes in pre- and post-ganglionic sympathetic nerve activity that imply that NO serves to inhibit central sympathetic outflow. There is also evidence that NO may attenuate cardiovascular end-organ responses to sympathetic stimulation. Studies suggest that NO modulates cardiac vagal control, increasing the activity of central vagal motoneurons and, more contentiously, contributing to the bradycardic effects of vagal stimulation. NO also modulates so-called ‘indirect’ vagal inhibition of sympathetic cardiac responses. Additionally, central attenuation of baroreflex-mediated vagal control has been described. There is relatively little information available on the importance of NO in the regulation of human cardiovascular autonomic control. Further well-controlled studies are required.

Role of nitric oxide in the regulation of cardiovascular autonomic control

Alteration in function of the cardiac autonomic nervous system has proved to be a powerful predictor of cardiac death or serious arrhythmia in patients with cardiac disease, yet little is known about the mechanisms by which this system is regulated. Recent evidence suggests that the gaseous molecule nitric oxide (NO) may act as an important mediator in this pathway. Histochemical staining techniques have identified neuronal populations that contain NO synthase within medullary cardio-regulatory sites and their peripheral autonomic pathways. Drugs that modulate the NO pathway (administered both systemically and into the central nervous system) cause changes in pre- and post-ganglionic sympathetic nerve activity that imply that NO serves to inhibit central sympathetic outflow. There is also evidence that NO may attenuate cardiovascular end-organ responses to sympathetic stimulation. Studies suggest that NO modulates cardiac vagal control, increasing the activity of central vagal motoneurons and, more contentiously, contributing to the bradycardic effects of vagal stimulation. NO also modulates so-called 'indirect' vagal inhibition of sympathetic cardiac responses. Additionally, central attenuation of baroreflex-mediated vagal control has been described. There is relatively little information available on the importance of NO in the regulation of human cardiovascular autonomic control. Further well-controlled studies are required.

Differential control of renal vs. adrenal sympathetic nerve activity by NTS A2a and P2x purinoceptors.

Activation of adenosine A2a and ATP P2x purinoceptors in the subpostremal nucleus tractus solitarii (NTS) via microinjection of the selective agonists CGS-21680 and alpha,beta-methylene ATP (alpha, beta-MeATP), respectively, elicits large dose-dependent decreases in arterial pressure and heart rate, differential regional vasodilation, and differential inhibition of regional sympathetic outputs. With marked hypotensive hemorrhage, preganglionic adrenal sympathetic nerve activity (pre-ASNA) increases, whereas renal (RSNA) and postganglionic adrenal sympathetic nerve activity (post-ASNA) decrease. In this setting, adenosine levels in the brain stem increase. Therefore, we investigated whether stimulation of specific purinoceptors in the NTS may evoke differential sympathetic responses. RSNA was recorded simultaneously with pre-ASNA or post-ASNA in chloralose-urethan-anesthetized male Sprague-Dawley rats. CGS-21680 (2 and 20 pmol in 50 nl) inhibited RSNA and post-ASNA, whereas pre-ASNA increased markedly. alpha,beta-MeATP (25 and 100 pmol in 50 nl) inhibited all sympathetic outputs. Sinoaortic denervation plus vagotomy markedly prolonged the responses to P2x-purinoceptor stimulation. Glutamate (100 pmol in 50 nl) caused differential inhibition of all sympathetic outputs similar to that evoked by alpha,beta-MeATP. We conclude that NTS A2a-purinoceptor activation evokes differential sympathetic responses similar to those observed during hemorrhage, whereas P2x-purinoceptor and glutamate-receptor activation evokes differential inhibition of sympathetic outputs similar to arterial baroreflex responses.