Pattern Of Sympathetic Nerve Activity Research Articles

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model.

The paraventricular nucleus of the hypothalamus (PVN) contains premotor neurons involved in the control of sympathetic vasomotor activity. It is known that the stimulation of specific areas of the PVN can lead to distinct response patterns at different target territories. The underlying mechanisms, however, are still unclear. Recent evidence from sympathetic nerve recording suggests that relevant information is coded in the power distribution of the signal along the frequency range. In the present study, we addressed the hypothesis that the PVN is capable of organizing specific spectral patterns of sympathetic vasomotor activation to distinct territories in both normal and hypertensive animals. To test it, we investigated the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), before and after disinhibition of the PVN by bicuculline microinjection. Subjects were control and Goldblatt rats, a sympathetic overactivity-characterized model of neurogenic hypertension (2K1C). Additionally, considering the importance of angiotensin II type 1 receptors (AT1) in the sympathetic responses triggered by bicuculline in the PVN, we also investigated the impact of angiotensin AT1 receptors blockade in the spectral features of the rSNA and sSNA activity. The results revealed that each nerve activity (renal and splanchnic) presents its own electrophysiological pattern of frequency-coded rhythm in each group (control, 2K1C, and 2K1C treated with AT1 antagonist losartan) in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the losartan 2K1C treated group showed no decrease in the hypertensive response triggered by bicuculline when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups (control and 2K1C), suggesting that the blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic responses nor the electrophysiological patterns in Goldblatt rats, but act on their spectral frequency distribution. The results suggest that the differential responses evoked by the PVN were preferentially coded in frequency, but not in the global power of the vasomotor sympathetic responses, indicating that the PVN is able to independently control the frequency and the power of sympathetic discharges to different territories.

Abstract 17981: Decreased Oscillatory Pattern of Sympathetic Nerve Activity is Associated With Arterial Baroreflex Dysfunction in Chronic Heart Failure Patients

Background: Sympathetic activation and arterial baroreflex (ABR) dysfunction typify chronic heart failure (CHF). In addition, decreased oscillatory pattern of muscle sympathetic nerve activity (MSNA, LF MSNA /HF MSNA ) seems to contribute to sympathetic exacerbation in patients with CHF. Unknown is whether the LF MSNA /HF MSNA is associated with ABR dysfunction in CHF patients. To answer this question, we investigated the association between gain, latency and coupling of ABR function and LF MSNA /HF MSNA in CHF patients. Methods and Results: Forty-three CHF patients, Functional Class II to III, NYHA, ejection fraction ≤40% were allocated into two groups according to the level of LF MSNA /HF MSNA index: 1) Higher LF MSNA /HF MSNA (n=21, 52±2 years) and 2) Lower LF MSNA /HF MSNA (n=22, 54±1 years). Blood pressure (BP, oscillometric beat-to-beat basis) and MSNA (microneurography technique) were recorded during 10 min at rest. Spectral and cross-spectral analyses of BP and MSNA variabilities were conducted to assess the LF MSNA /HF MSNA and the gain, latency and coupling between BP and MSNA of ABR function. Etiology, ejection fraction, gain and latency of ABR function were similar between groups. However, the patients with lower LF MSNA /HF MSNA had increased MSNA bursts frequency (53±2vs. 39±3 bursts/min, P<0.01) and total activity (180±15 vs. 126±17 a.u, P=0.03) compared to the patients with higher LF MSNA /HF MSNA . In contrast, the patients with lower LF MSNA /HF MSNA had reduced coupling of ABR function (69±3 vs. 80±2 %, P<0.01). Further analysis showed a significant association between the coupling of ABR function and LF MSNA /HF MSNA (R=0.36, P=0.02). Conclusions: There is an inverse association between the LF MSNA /HF MSNA index and sympathetic nerve activity. In addition, there is a direct association between the LF MSNA /HF MSNA index and the coupling of ABR, which suggests that the ABR dysfunction explains, at least in part, the augmented sympathetic nerve activity in CHF patients.

Firing patterns of muscle sympathetic neurons during short-term use of continuous positive airway pressure in healthy subjects and in chronic heart failure patients

The current study tested the hypothesis that modification in central hemodynamics during short-term continuous positive airway pressure (CPAP) application was accompanied by altered firing patterns of sympathetic nerve activity in CHF patients and healthy subjects.Muscle sympathetic nerve activity (MSNA), hemodynamic and ventilatory parameters were obtained from 8 healthy middle aged subjects and 7 CHF patients. Action potentials (APs) were extracted from MSNA neurograms, quantified as AP frequency and classified into different sized clusters. While on CPAP at 10cm H2O, multi-unit MSNA, AP frequency and mean burst area/min increased in healthy middle aged subjects (p<0.05) whereas CPAP had no effect on these variables in CHF patients. In conclusion, the impact of CPAP on central hemodynamics in healthy individuals elicited a moderate activation of sympathetic neurons through increased AP firing frequency, whereas in CHF patients both hemodynamics and MSNA remained unaltered.

Blood Pressure and Sympathetic Nerve Tone Relation during Hemodialysis may Reflect Cardiovascular Dysfunction

The blood pressure response to the rapid removal of fluid during hemodialysis is complex and the pathophysiological mechanisms underlying intradialytic hypotension are not clear and sometimes these mechanisms render dialysis difficult to continue. We analyzed the changes in blood pressure and sympathetic nerve tone and attempted to clarify whether the dynamic pattern of this relationship reflects cardiovascular dysfunction. The dynamic pattern of sympathetic nerve activity throughout dialysis was analyzed by frequency analysis of RR intervals recorded by 24 hours Holter electrocardiography in 64 patients and 3 minutes ECG every 15 minutes during dialysis in 121 stable end-stage renal failure patients who underwent maintenance hemodialysis. Blood pressure and fluid volume removed was measured every 15-30 minutes during dialysis and the average value of the ratio of low to high frequency components (LF/HF) was calculated as an index of sympathetic nerve tone. The relationship between removed fluid volume, systolic blood pressure (Bp) and LF/HF was analyzed. The patients were classified into 3 groups based on the correlation between the LF/HF and Bp as follows: positive (52 cases), inverse (54 cases), and not significant (NS; 61 cases). Eighteen patients who showed multiple arrhythmias, atrial fibrillation and other artifacts or noises were eliminated as they were inadequate for frequency analysis of RR intervals. The positive group was characterized by a hypotension-resistant response with a low LF/HF, whereas the inverse group was characterized by a hypotension-prone response with high LF/HF. These results suggest that cardiovascular dysfunction is responsible for the inverse correlation. Analysis of the relationship between sympathetic nerve tone and Bp is effective in predicting the existing of cardiovascular dysfunction.

Tyrosine hydroxylase immunoreactivity as indicator of sympathetic activity: simultaneous evaluation in different tissues of hypertensive rats

Vasomotor control by the sympathetic nervous system presents substantial heterogeneity within different tissues, providing appropriate homeostatic responses to maintain basal/stimulated cardiovascular function both at normal and pathological conditions. The availability of a reproducible technique for simultaneous measurement of sympathetic drive to different tissues is of great interest to uncover regional patterns of sympathetic nerve activity (SNA). We propose the association of tyrosine hydroxylase immunoreactivity (THir) with image analysis to quantify norepinephrine (NE) content within nerve terminals in arteries/arterioles as a good index for regional sympathetic outflow. THir was measured in fixed arterioles of kidney, heart, and skeletal muscle of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (123 ± 2 and 181 ± 4 mmHg, 300 ± 8 and 352 ± 8 beats/min, respectively). There was a differential THir distribution in both groups: higher THir was observed in the kidney and skeletal muscle (∼3-4-fold vs. heart arterioles) of WKY; in SHR, THir was increased in the kidney and heart (2.4- and 5.3-fold vs. WKY, respectively) with no change in the skeletal muscle arterioles. Observed THir changes were confirmed by either: 1) determination of NE content (high-performance liquid chromatography) in fresh tissues (SHR vs. WKY): +34% and +17% in kidney and heart, respectively, with no change in the skeletal muscle; 2) direct recording of renal (RSNA) and lumbar SNA (LSNA) in anesthetized rats, showing increased RSNA but unchanged LSNA in SHR vs. WKY. THir in skeletal muscle arterioles, NE content in femoral artery, and LSNA were simultaneously reduced by exercise training in the WKY group. Results indicate that THir is a valuable technique to simultaneously evaluate regional patterns of sympathetic activity.

Sympathetic nerve activity has more character than you may think

Sympathetic nerve activity has more character than you may think

Every breath you take: why sympathetic nerve activity comes in bursts.

In this issue of The Journal of PhysiologyMandel & Schreihofer (2009) investigate the source of the hypoxia-related effects on sympathetic nerve activity. Hypoxia causes a profound change in the pattern of sympathetic nerve activity. Normally in an anaesthetized and paralysed preparation, sympathetic nerve activity is characterized by bursts of activity that tend to be grouped in phase with the pulse (baroreceptor modulated) and with respiration (generally an inspiratory and a post-inspiratory burst). These patterns occur on a background of activity that is generally referred to as ‘tone’. The source of sympathetic tone is still a matter for discussion, but is not the topic of the findings of Mandel & Schreihofer (2009) who have focused on the change in sympathetic activity in hypoxia. It is well known that supra-threshold activation of baroreceptor afferent neurons will cause sympathetic nerve activity to stop completely. This finding implies that the ongoing activity in sympathetic nerves is due to vasoconstrictor-type fibres and that others are silent. Here we find strong circumstantial evidence that the silent period between bursts of activity is mediated by activation of the same caudal ventrolateral medulla (CVLM) neurons that are GABAergic inhibitory interneurons and project to the rostral ventrolateral medulla (RVLM). This finding is novel and important. It suggests that while the neurons in the RVLM play a role in integrating inputs to provide a final excitatory output to sympathetic preganglionic neurons, the neurons in the CVLM play the opposite but equally important integrating role to inhibit sympathetic discharge. This excitation/inhibition phenomenon as a consequence of RVLM/CVLM interaction is well established in baroreceptor function (potent baroreceptor excitation will silence RVLM neurons) but is less well established in other situations where sympathetic bursting occurs. What are the implications for the normal physiological function of this interaction? As shown by Mandel & Schreihofer (2009) the change to a prolonged burst pattern is associated with marked fluctuations in arterial blood pressure. It remains to be seen if the same mechanism can explain similar phenomena such as the pressor and sympathoexcitatory responses seen after swallowing (Matsukawa & Ninomiya, 1987). In the paralysed anaesthetized ventilated cat, the inspiration-synchronous component of sympathetic discharge was estimated at about 25%; in situations such as that described here it is presumably considerably greater. Clinically, the respiratory modulation of sympathetic nerve activity is also likely to be of importance. Clonidine has a well-known potent sympatholytic effect that is responsible for its efficacy as a hypotensive agent. This effect of clonidine is achieved by a selective action to reduce tone, and the post-inspiratory peak in activity without affecting the inspiratory peak in activity (Koshiya & Guyenet, 1995); interestingly, the effect of clonidine parallels that of Ni2+ which also reduces tone but does not block respiratory activity (or other reflexes) (Miyawaki et al. 2003). Brainstem cardiovascular neurons are close to (Pilowsky et al. 1990) and probably influenced directly by (Sun et al. 1997) respiratory neurons. Such inputs are the most likely explanation for the respiratory modulation of sympathetic nerves (Pilowsky et al. 1994), presympathetic nerves (Haselton & Guyenet, 1989; Miyawaki et al. 1995) and GABAergic CVLM interneurons of the type studied in the current paper (Mandel & Schreihofer, 2006). The precise functional and structural relationship of respiratory and cardiovascular neurons remains an important area of investigation.

Sympathetic neurogenic Ca2+ signalling in rat arteries: ATP, noradrenaline and neuropeptide Y

The sympathetic nervous system (SNS) plays an essential role in the control of total peripheral vascular resistance by controlling the contraction of small arteries. The SNS also exerts long-term trophic influences in health and disease; SNS hyperactivity accompanies most forms of human essential hypertension, obesity and heart failure. At their junctions with smooth muscle cells, the peri-arterial sympathetic nerves release ATP, noradrenaline (NA) and neuropeptide Y (NPY) onto smooth muscle cells. Confocal Ca(2+) imaging studies reveal that ATP and NA each produce unique types of postjunctional Ca(2+) signals and consequent smooth muscle cell contractions. Neurally released ATP activates postjunctional P2X(1) receptors to produce local, non-propagating Ca(2+) transients, termed 'junctional Ca(2+) transients', or 'jCaTs'. Neurally released NA binds to alpha(1)-adrenoceptors and can activate Ca(2+) waves or more uniform global changes in [Ca(2+)]. Neurally released NPY does not appear to produce Ca(2+) transients directly, but significantly modulates NA-induced Ca(2+) signalling. The neural release of ATP and NA, as judged by postjunctional Ca(2+) signals, electrical recording of excitatory junction potentials and carbon fibre amperometry to measure NA, varies markedly with the pattern of nerve activity. This probably reflects both pre- and postjunctional mechanisms, which are not yet fully understood. These phenomena, together with different temporal patterns of sympathetic nerve activity in different regional circulations, are probably an important mechanistic basis of the important selective regulation of regional vascular resistance and blood flow by the sympathetic nervous system.

Paraventricular Neurones Elicit a Volume Expansion‐Like Change of Activity in Sympathetic Nerves to the Heart and Kidney in the Rabbit

The role of the paraventricular nucleus (PVN) of the hypothalamus in the cardiovascular response induced by blood volume expansion was examined in anaesthetised rabbits, in which simultaneous recordings were made from a renal sympathetic nerve and one of other sympathetic nerves, the inferior cardiac nerve, a splanchnic nerve and an adrenal nerve. Activation of PVN neurones, by discrete injections (25-100 nl) of d,l-homocysteic acid (DLH, 0.2 M) produced one main pattern of sympathetic nerve activity accompanying a pressor response (57-86 % of PVN sites). This was a decrease in renal sympathetic activity (27 +/- 12 %) and an increase in splanchnic (60 +/- 12 %), adrenal (31 +/- 9 %) and cardiac (42 +/- 8 %) sympathetic activity. Sites in the PVN from which these combinations of nerve activity were obtained were not confined to a specific subnucleus. An increase in renal sympathetic activity which was reversed to a decrease by reducing the volume of DLH injected was obtained at 10 sites in the PVN. These sites were mainly located in the dorsal parvocellular subnucleus. Varying combinations of sympathetic activation were obtained at a minority of sites. It is concluded that the PVN can evoke a differential pattern of sympathetic discharge which may be functionally significant in the control of blood volume regulation, as it mimics that seen on acute volume expansion.

Paraventricular neurones elicit a volume expansion-like change of activity in sympathetic nerves to the heart and kidney in the rabbit

The role of the paraventricular nucleus (PVN) of the hypothalamus in the cardiovascular response induced by blood volume expansion was examined in anaesthetised rabbits, in which simultaneous recordings were made from a renal sympathetic nerve and one of other sympathetic nerves, the inferior cardiac nerve, a splanchnic nerve and an adrenal nerve. Activation of PVN neurones, by discrete injections (25-100 nl) of d,l-homocysteic acid (DLH, 0.2 M) produced one main pattern of sympathetic nerve activity accompanying a pressor response (57-86% of PVN sites). This was a decrease in renal sympathetic activity (27 +/− 12%) and an increase in splanchnic (60 +/− 12%), adrenal (31 +/− 9%) and cardiac (42 +/− 8%) sympathetic activity. Sites in the PVN from which these combinations of nerve activity were obtained were not confined to a specific subnucleus. An increase in renal sympathetic activity which was reversed to a decrease by reducing the volume of DLH injected was obtained at 10 sites in the PVN. These sites were mainly located in the dorsal parvocellular subnucleus. Varying combinations of sympathetic activation were obtained at a minority of sites. It is concluded that the PVN can evoke a differential pattern of sympathetic discharge which may be functionally significant in the control of blood volume regulation, as it mimics that seen on acute volume expansion.

Renal nerve responses to somatic nerve activation in stroke-prone spontaneously hypertensive rats

In chloralose/urethane anaesthetised stroke-prone spontaneously hypertensive rats, blood pressure and integrated renal nerve activity were higher whereas heart rate was lower than in Wistar rats by 37, 146 and 11%, respectively (all P<0.001). The renal nerve signal was subjected to fast Fourier transformation to generate power spectra. In the hypertensive rats, total spectral power was 400% ( P<0.01) and power at the heart rate frequency was 50% ( P<0.01) greater while phase and time differences were shorter (both P<0.001) than in Wistar rats. Brachial nerve stimulation increased total power in Wistar and hypertensive rats ( P<0.05), but importantly, power at the heart rate frequency was decreased by 80% in Wistar whereas there was a 20% ( P<0.05) increase in hypertensive rats, while phase and time differences were raised only in hypertensive rats ( P<0.05). Bilateral cervical vagotomy of the hypertensive rats had minimal actions on most variables but phase and time differences were doubled compared to intact hypertensive animals, but brachial nerve stimulation decreased power at the heart rate frequency ( P<0.05) which was a very different response from intact rats. Resting blood pressure, heart rate, total power and power at the heart rate frequency in the carotid sinus denervated animals were lower than in intact hypertensive rats, between 17 and 71%, respectively, but increased during brachial nerve stimulation. These experiments demonstrated that whereas somatic sensory input can modulate the pattern of sympathetic nerve activity to the kidney under normal conditions, this does not occur in the hypertensive rat. This appears to be related to afferent information carried by the vagus which suppresses the normal response; the carotid sinus baroreceptors are devoted to organising the nerve activity in relation to the blood pressure pulse wave.

Respiratory‐related discharge pattern of sympathetic nerve activity in the spontaneously hypertensive rat.

1. Synchronization of spontaneous sympathetic discharge during the respiratory cycle was studied in the cervical and renal nerves of vagotomized, normotensive Wistar-Kyoto rats (WKYs) and age-matched spontaneously hypertensive rats (SHRs). Phrenic nerve discharge was used as an index of central inspiratory activity. 2. In normotensive Wistar-Kyoto rats depression of sympathetic activity appeared at the onset of inspiration reaching a minimum at mid-inspiration. Peak maximal sympathetic discharge corresponded to postinspiratory phase; a second increase sometimes appeared in late expiration. Variations of respiratory frequency over wide range of experimental conditions by hypoxia, hyperoxia, hyper- or hypocapnia and transection of carotid sinus nerves did not affect this pattern. 3. In SHRs the respiratory-phase-related timing of sympathetic discharge was variable. In normoxia, the maximal sympathetic activity occurred in late inspiration, preceded by short depression at early inspiration and followed by postinspiratory depression. A second increase in sympathetic activity was observed in mid-expiration. 4. The pattern of respiratory phase modulated sympathetic activity in SHRs was altered by hypoxic stimulation of the peripheral chemoreceptors. The early inspiratory depression of sympathetic activity was substantially prolonged and the maximal sympathetic discharge was shifted from inspiration to early expiration. This effect was abolished after carotid sinus nerves had been cut. 5. Hypercapnic stimulation of central chemoreceptors in SHRs with carotid sinus nerves cut did not influence the timing of the sympathetic activity in relation to the respiratory phase, though the magnitude of rhythmical sympathetic discharges was increased. 6. We discuss the possibility that altered synchronization between central respiratory drive and sympathetic neuronal system may contribute to the neurogenic mechanisms of arterial hypertension in SHRs.

A ventromedullary relay involved in the hypothalamic and chemoreceptor activation of sympathetic postganglionic neurones to skeletal muscle, kidney and splanchnic area

Bilateral application of glycine to the ventral surface of the medulla produces a profound hypotension during which sympathetic vasoconstrictor activity to splanchnic, renal and skeletal muscle vascular beds is reduced. The pattern of activation of sympathetic vasoconstrictor fibres to kidney and skeletal muscle, during carotid chemoreceptor activation and hypothalamic stimulation, is attenuated as tonic sympathetic activity diminishes. Functioning ventromedullary neurones are thus necessary for maintaining tonic sympathetic nerve activity, and for reflex and brain evoked patterns of sympathetic nerve activity, in the anaesthetized cat.