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H Seller

Publications and source records attributed to H Seller.

At least 37 records · Page 2Linked to original sources
PubMed1995

Inhibition of basal and reflex-mediated sympathetic activity in the RVLM by nitric oxide.

We examined possible functional roles for nitric oxide (NO) in the rostral ventrolateral medulla (RVLM), which is the final area for integration of sympathetic nerve activity (SNA) within the brain stem. Chloralose-anesthetized cats were completely baro- and chemoreceptor denervated, the RVLM was exposed for microinjections, and preganglionic SNA was recorded from the white ramus of the 3rd thoracic segment. Injections of NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, but not of NG-nitro-D-arginine, caused distinct increases in SNA and arterial blood pressure (BP). Excitatory somatosympathetic reflex amplitudes evoked by electrical stimulation of the 4th intercostal nerve were significantly increased by L-NNA whereas inhibitory responses to baroreflex activation by stimulation of the carotid sinus nerve were not affected. The effects of L-NNA were counteracted by the NO-donor compounds glyceryltrinitrate and S-nitroso-N-acetylpenicillamine, which decreased BP and SNA below control values at higher doses. These results suggest that endogenous NO, in addition to its peripheral actions, modulates the central nervous control of cardiovascular functions by reduction of basal sympathetic tone and by attenuation of excitatory reflex responses.

Animals↗
PubMed1994

Excitatory somato-sympathetic reflexes are relayed in the caudal ventrolateral medulla in the cat.

The caudal ventrolateral medulla (CVLM) modulates sympathetic outflow from the rostral ventrolateral medulla (RVLM). We studied the possible role of the CVLM in the transmission of excitatory somato-sympathetic reflexes in baro- and chemoreceptor denervated chloralose-anesthetized cats. Neurotoxic doses of kainate, injected in the CVLM, caused marked increases in baseline sympathetic nerve activity (SNA) and arterial blood pressure (BP). Concomitantly, excitatory somato-sympathetic reflex responses evoked by electrical stimulation of the 4th intercostal nerve disappeared almost completely. Similar effects on SNA and BP but not on somato-sympathetic reflexes were observed when the GABA-antagonist bicuculline was injected in the RVLM. Bicuculline injected in the RVLM after kainate had no additional effects. These results suggest that in addition to a tonic GABA-ergic inhibition on the RVLM, the CVLM controls somato-sympathetic reflex transmission through interneurons located in this region.

Animals↗
PubMed1994

Somato-sympathetic reflex transmission in the ventrolateral medulla oblongata: spatial organization and receptor types.

Tonic sympathetic activity in vivo is continuously modulated by inhibitory and excitatory reflex mechanisms. We studied the properties of somato-sympathetic excitatory reflex transmission in the rostral ventrolateral medulla (RVLM) of baroreceptor-denervated and vagotomized chloralose-anesthetized cats. Electrical stimulation of the left intercostal nerve of the 4th thoracic segment (IC-T4) elicited an early spinal and a late supraspinal reflex in the ipsilateral white ramus T3 from which recordings were made. Bilateral cooling of the ventral surface of the RVLM reversibly reduced the supraspinal reflex amplitude to 18.0 +/- 3.1% of control (100%). The spinally evoked reflex was enhanced to maximally 154.7 +/- 5.3%. Cooling of only the ipsilateral side of the RVLM was nearly equieffective in both, suppressing the supraspinal and enhancing the spinal reflex component. In contrast, cooling of the contralateral side had no significant effects on supraspinal reflex transmission but caused slight increases of the spinal reflex amplitudes. Similar effects were obtained by microinjection (RVLM) of the glutamate antagonist kynurenic acid (5 x 10(-3) M, n = 7) and the specific non-NMDA receptor antagonist CNQX (4 x 10(-3) M, n = 4) which, however, blocked the supraspinal reflex less effectively. These results demonstrate that the RVLM represents an essential relay in the transmission of both somatosympathetic reflex components. The experiments further suggest an almost completely ipsilateral neuronal pathway for the supraspinal reflex component which projects from the RVLM to the intermediolateral cell column (IML). The descending inhibition of the spinal reflex, however, receives neuronal inputs from the contralateral side.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Different effects of respiratory and metabolic acidosis on preganglionic sympathetic nerve activity.

We studied sympathetic nerve activity (SNA) responses, recorded in multifiber preparations of left third thoracic white ramus, to respiratory or isocapnic metabolic acidosis or to CO2 enhancement at constant pH in chloralose-anesthetized paralyzed artificially ventilated cats. Cardiopulmonary, baro-, and peripheral chemoreceptors were denervated by bilaterally cutting vagus and carotid sinus nerves. Acidosis was induced by either decreasing artificial ventilation or infusing HCl (0.5 M i.v.). Both respiratory and isocapnic metabolic acidosis induced a decrease in local extracellular pH, measured directly with pH-sensitive microelectrodes within medulla region containing sympathoexcitatory bulbospinal neurons. The magnitude of changes in medullary pH was independent of the way systemic acidosis was generated. Despite uniformity of changes in local medullary extracellular pH due to systemic respiratory or isocapnic metabolic acidosis, different responses were observed in preganglionic SNA. Isocapnic metabolic acidosis resulted in a slight increase in SNA, averaging 6.4% per 0.05 systemic pH unit decrease. In contrast, respiratory acidosis induced by decreasing artificial ventilation produced a more pronounced increase of SNA, reaching peak changes of approximately 70% compared with control level with normal blood gases, an average increase of 13% per 0.05 systemic pH unit decrease. We conclude that systemic CO2 and H+ concentrations represent different stimuli to sympathetic nervous system. Despite similar changes of local extracellular pH within rostral ventrolateral medulla during systemic acidosis, different responses of SNA suggest other sites or as yet unknown additional effects of CO2 as being responsible for excitation of sympathetic activity.

Acidosis↗
PubMed1994

Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo.

The objective of this study was to determine whether vasodilator effects of nitric oxide (NO) can be explained by the inhibition of vasoconstriction caused by peripheral sympathetic nerve activity (SNA) in vivo. For this purpose, we studied the effects of systemic inhibition of NO synthesis during experimental variation of SNA in anesthetized cats. Intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) in baroreceptor-intact animals (n = 6) caused increases in mean arterial blood pressure (MAP) from 105.8 +/- 3.4 to 192.0 +/- 4.3 mm Hg that were associated with slight decreases in preganglionic SNA recorded from the white ramus of the third thoracic segment. Higher SNA appeared in completely baroreceptor-denervated cats (n = 10) than in the intact cats, but no changes in nerve activity occurred after the subsequent administration of L-NAME. In contrast, MAP increased from 123.3 +/- 4.0 to 245.8 +/- 5.1 mm Hg. In baroreceptor-denervated cats, reversible suppression of peripheral SNA produced by cooling of the ventral surface of the rostral ventrolateral medulla oblongata (RVLM) caused significant hypotension (61.1 +/- 2.6 mm Hg) and almost completely reversed the hypertension caused by L-NAME (76.0 +/- 3.7 mm Hg). Intravenous administration of the alpha 1-adrenergic receptor antagonist prazosin after L-NAME reduced MAP to a similar extent. In contrast, hypertension induced by angiotensin II could not be reversed by RVLM cooling. The pressor effects of intravenously administered noradrenaline during RVLM cooling were markedly potentiated by L-NAME and attenuated by the NO-donor compound S-nitroso-N-acetylpenicillamine (SNAP).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Central action of alpha-adrenoceptor agents on the baroreceptor reflex.

In chloralose-anaesthetized cats the effects of intravenous application of the alpha 1- and alpha 2-adrenoceptor agonistic and antagonistic agents methoxamine, prazosin, B-HT 933 and rauwolscine were tested on baroreceptor reflex, sympathetic background activity and blood pressure. Sympathetic activity was recorded from the renal nerve and the efficacy of the central transmission of the baroreceptor reflex was measured by the duration of the complete inhibition of renal nerve activity during electrical stimulation of the left carotid sinus nerve. All baroreceptors were denervated by sectioning both carotid sinus and vagal nerves. The alpha 1-agonist methoxamine increased baroreceptor-induced sympatho-inhibition, sympathetic background activity and blood pressure. The alpha 1-antagonist prazosin had the opposite effects. The alpha 2-agonist B-HT 933 was most effective in augmenting the inhibitory response in sympathetic activity to baroreceptor stimulation; sympathetic background activity and blood pressure were also decreased. At low doses (50 micrograms/kg) the alpha 2-antagonist rauwolscine reduced the baroreceptor sympathetic reflex inhibition and increased sympathetic activity and blood pressure. The effect of B-HT 933 upon the baroreceptor reflex could be completely antagonized by rauwolscine. These findings demonstrate a very effective facilitation of the baroreceptor reflex transmission by stimulation of central alpha 2-adrenoceptors. Through such humoral-neuronal interaction circulating catecholamines are likely to modulate cardiovascular control.

Adrenergic alpha-Agonists↗
PubMed1992

Cardiac sympathetic nervous activity during myocardial ischemia, reperfusion and ventricular fibrillation in the dog--effects of intravenous lidocaine.

In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after occlusion of the left anterior descending coronary artery as well as during reperfusion and ventricular fibrillation (VF). In 7 control animals, CSNA did not significantly differ from preocclusion levels when determined 20 min after occlusion (+3.5 +/- 1.5%, mean +/- SEM) and up to 15 min following reperfusion (+1.5 +/- 0.6%). However, VF was associated with a potential increase in CSNA by 106 +/- 15.5% (p less than 0.001). The effect of lidocaine (6 mg/kg) on cardiac sympathetic tone was examined in 5 additional animals. Lidocaine reduced control CSNA by 23 +/- 4.7% (p less than 0.001); subsequent ischemia and reperfusion did not substantially change the level of preocclusion activity. CSNA decreased significantly also during VF (52 +/- 4.2%, p less than 0.001). In conclusion, efferent CSNA was slightly altered in the course of acute myocardial ischemia and reperfusion, but significantly increased during VF. Lidocaine produced marked attenuation of CSNA in anesthetized dogs.

Animals↗
PubMed1991

Historical development of current concepts on central chemosensitivity.

The history of concepts on the mechanism of central chemosensitivity is reviewed with special emphasis on ideas that have remained valid or stimulating until today. Early physiologists considered chemoreception to be a property of respiratory neurones in the brainstem (Pflüger 1868; Gesell 1926, 1949; Winterstein 1910, 1921, 1956). It has not been elucidated by which mechanism acid/base disturbances cause cardiorespiratory adaption. The reaction theory focused on protons as being the decisive stimulus (Lehmann 1888, Winterstein 1921, Loeschcke 1982), but this issue can be adequately discussed only when the compartment where changes occur is taken into account (Jacobs 1920, Gesell 1940). Heymans and collaborators demonstrated in 1930 that chemoreception is not only possible by a central mechanism but also at the level of the peripheral chemoreceptors. Without solid evidence for such an assumption, the existence of specific 'receptors' for pH and/or pCO2 was postulated by von Euler and Söderberg in 1952. Several chemosensitive areas at the ventrolateral surface of the medulla oblongata were defined by Loeschcke and collaborators in a series of papers after 1958. Within these areas, however, a specific chemoreceptor has not been distinguished. On the other hand, a direct chemosensitivity of bulbospinal sympathoexcitatory neurones as an intrinsic property of these neurones has recently been demonstrated (Seller 1989). Therefore, coming back to the original concept of chemoreception as a function of central cardio-respiratory neurones appears to be the most promising path for future research.

Animals↗
PubMed1990

Chemosensitivity of sympathoexcitatory neurones in the rostroventrolateral medulla of the cat.

The hypothesis that sympathoexcitatory neurones within the rostroventrolateral medulla (RVLM) may be chemosensitive was tested in chloralose-anaesthetized cats by artificial perfusion of the RVLM via the left vertebral artery. The baroreceptors and peripheral chemoreceptors were denervated by bilaterally dissecting the carotid sinus and vagus nerves. Either white ramus T3 (WR-T3) or the renal nerve was recorded to monitor sympathetic activity. Perfusion with saline or Ringer solution bubbled with CO2 (10%-100%) produced a rapid and pronounced increase in sympathetic activity and blood pressure. Solutions adjusted to the same pH (pH 5.2 for 100% CO2) with HCl resulted in a much weaker excitation. A linear relationship between PCO2 and sympathetic activity was demonstrated. During prolonged perfusion (90 s) sympathetic activity returned to the control level after initial excitation and fell below control levels when perfusion ceased. The sympathetic activity response to CO2-bubbled solutions was unaffected by blockade of synaptic input by microinjection of CoCl2 into the RVLM, whereas spontaneous sympathetic activity and the supraspinal somato-sympathetic reflex from intercostal nerve T4 to WR-T3 were markedly reduced. It is therefore concluded that sympathoexcitatory bulbospinal neurones in the RVLM are directly chemosensitive to changes in arterial PCO2 and pH.

Animals↗
PubMed1990

Glucose utilization, blood flow and capillary density in the ventrolateral medulla of the rat.

A specific population of neurons in the ventrolateral medulla (VLM) acts as the main integration center for the regulation of the sympathetic outflow to the cardiovascular system. In order to investigate whether this nucleus can be distinguished from its surroundings in the reticular formation of the medulla with respect to functional and morphological variables, the present study investigates several of such variables in this area on a quantitative basis. Local medullary glucose utilization was measured by the 2-[14C]deoxyglucose method; local medullary blood flow was quantified using iodo[14C]-antipyrine, and the local density of perfused capillaries was calculated by counting the number of intravascular fluorescent spots in brain sections after i.v. infusion of a globulin-coupled fluorescent dye. The values obtained from the VLM were compared with the respective values found in a reference area of the same brain section (gigantocellular nucleus). The values for glucose utilization, blood flow and capillary density were significantly (P less than 0.05) higher in the VLM than in the reference area (gigantocellular nucleus). This difference was 44.7% for glucose utilization, 34.1% for blood flow and 19.7% for capillary density. These data support the hypothesis that neurons in the VLM are specifically well supplied for being directly regulated in their activity by the PCO2 and pH in the arterial blood.

Animals↗
PubMed1989

Chemoreceptor stimulation on sympathetic activity: dependence on respiratory phase.

Experiments were performed on chloralose-anesthetized, vagotomized, paralyzed, and artificially ventilated cats breathing 100% O2. Peripheral chemoreceptors were stimulated by rapid injections of CO2-saturated NaHCO3 in different phases of the respiratory cycle. Responses of cardiac and renal sympathetic nerves were computed by digital integration. Spontaneous sympathetic activity was consistently modulated by respiration, the modulation being greater for cardiac than for renal nerves. Cardiac nerve responses to peripheral chemoreceptor stimulation depended on the respiratory phase for at least one experimental condition in four of seven animals: the responses were largest during late inspiration and smallest (or absent) during postinspiration and early expiration. Renal nerve responses depended on respiratory phase in only two of eight animals. An average end-tidal CO2 concentration increase from 4.6 +/- 0.8% (SD) to 6.7 +/- 0.9% enhanced the respiratory modulation of spontaneous activity but reduced the responses to peripheral chemoreceptor stimulation. The results indicate that the respiratory modulation of chemoreceptor-induced sympathetic responses was less prominent than the modulation of spontaneous activity. It is hypothesized that the phase dependence of the responses is caused by the spontaneously occurring expiratory diminution of sympathetic activity rather than by an inherent gating of the chemoreceptor reflex.

Animals↗
PubMed1989

Bepridil versus nifedipine for ventricular tachycardia induced in the late postinfarction phase in conscious dogs.

The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyarrhythmias were studied by programmed electrical stimulation in 15 dogs, 4-8 days after myocardial infarction. Recordings from the infarcted and normal anterior wall of the left ventricle were obtained with an epicardial implanted 'composite' electrode. Bepridil (5 mg/kg) or nifedipine (0.025 mg/kg) were administered i.v. on different days and testing was repeated. Sustained ventricular tachycardia was prevented or significantly slowed by bepridil in 11/12 experiments compared with none of 9 experiments with nifedipine. Paradoxically, in 10/15 dogs nifedipine accelerated arrhythmias or even provoked ventricular fibrillation. Bepridil prolonged refractoriness of infarcted myocardium by 15 +/- 4% (mean +/- SD, p less than 0.01), which was greater than the increase it produced in the effective refractory period of normal tissue (9.0 +/- 3.8%) or QTc interval (11 +/- 5.5%). In contrast, nifedipine significantly shortened these parameters. Both drugs did not influence conduction in infarcted and normal zones as indicated by unchanged late potentials, QRS duration and normal-zone electrograms, respectively. The data indicate that the antiarrhythmic action of bepridil was predominantly related to the prolongation of ventricular refractoriness and repolarization (class III effects).

Animals↗
PubMed1988

Effect of sino-aortic denervation in comparison to cardiopulmonary deafferentiation on long-term blood pressure in conscious dogs.

The isolated and combined influence of cardiopulmonary and sinoaortic denervation on long-term blood pressure (MAP), heart rate (HR), plasma renin activity (PRA) and plasma volume (PV) was studied in 11 conscious, chronically instrumented foxhounds receiving a normal sodium diet. MAP, HR, PV and PRA remained unchanged in the 5 dogs after bilateral thoracic vagal stripping, which eliminates the cardiopulmonary afferents. After sino-aortic denervation in another 5 dogs there was equally little change when compared to the control group. Only total baroreceptor and cardiopulmonary denervation (7 dogs) revealed significantly higher levels of MAP (119.6 +/- 4.6 vs. 100.4 +/- 1.5, P less than 0.01), HR (118.2 +/- 3.7; vs. 84.1 +/- 3.5; P less than 0.0001), and PRA (3.6 +/- 0.9 vs. 0.9 +/- 0.2; P less than 0.05). In conclusion, the function of either arterial baroreceptors or cardiopulmonary receptors is sufficient for normal circulatory control. When both groups of receptor afferents are interrupted, MAP, HR, and PRA rise to significantly higher levels. Thus, both systems interact in a sense of a non-additive attenuation on "cardiovascular centres". This may clarify previous disputes concerning neurogenic hypertension, and supplies information for the role of the renin-angiotensin system in blood pressure control.

Afferent Pathways↗
PubMed1988

Tonic descending inhibition of the spinal cardio-sympathetic reflex in the cat.

Electrical stimulation of the left inferior cardiac nerve elicited a two-component reflex potential (spinal and supraspinal reflexes) in the ipsilateral white ramus T3 from which recordings were made in chloralose-anaesthetised cats. Reversible interruption of all spinal pathways achieved by cooling the spinal cord at C2/C3 produced an enhancement of the spinal reflex and abolished the supraspinal reflex, the latter usually being the more prominent reflex potential prior to spinal cord block. The spinal cord block-induced increase in the amplitude of the spinal reflex was, however, less than the increase observed during stimulation of the somatic intercostal nerve T4. Recordings of the afferent volley following cardiac nerve stimulation and analysis of the stimulus-reflex response relationship in neuraxis-blocked cats indicated that the spinal reflex as determined here was activated by A delta afferent fibres. However, if stimulus strength was raised above C-fibre threshold, spinal cord block revealed in addition a late spinal reflex response. In some cases, the appearance of this late potential was accompanied by a secondary decline of the earlier spinal reflex potential, possibly indicating C-fibre-mediated afferent inhibition. Neither baroreceptor activation nor denervation had any effect on spinal reflex amplitudes. Pharmacologically, clonidine given i.v. to cats with a blocked neuraxis reduced the spinal reflex amplitudes to pre-block values, an action which could be antagonised by the subsequent administration of the alpha 2-adrenoceptor antagonist rauwolscine. When given to non-pretreated cats with intact neuraxis, however, neither rauwolscine nor its analog yohimbine were capable of inducing a persistent release from tonic inhibition. The results suggest that both purely visceral and somato-visceral reflexes are subject to tonic descending inhibition, but they do not support the hypothesis that a catecholamine is the responsible transmitter mediating this inhibition.

Adrenergic alpha-Antagonists↗
PubMed1988

Morphology of electrophysiologically identified baroreceptor afferents and second order neurones in the brainstem of the cat.

Baroreceptor afferent fibres and second order baroreceptor neurones were identified by their discharge pattern and were intracellularly injected with horseradish peroxidase. Three afferent fibres and three second order neurones were reconstructed by camera lucida drawings from serial sections of the brainstem. The afferent fibres were classified as A delta-fibres and had terminal arborizations with synaptic boutons in the dorsomedial region of the nuclei of the solitary tract (TS). The afferent fibres had additional collaterals with a medial projection to the commissural nucleus and in a direction lateral to the TS. The terminals of these collaterals could not be demonstrated. The second order neurones were located in the same dorsomedial region as the synaptic boutons of the afferent fibres. Neurones were small and spindle-shaped with two primary dendrites: one dendrite projected cranially along the medial border of the TS, and the second one projected caudally and medially into the commissural nucleus. The unmyalinated axons of these neurones could be traced over a distance of 1 mm. In only one neurone could an axon collateral be detected. The axons projected dorsally around the TS in a ventrolateral direction beyond the boundaries of the nuclei of the TS. The axon collateral projected in the medial direction into the commissural nucleus. In no case were axon terminals demonstrated.

Afferent Pathways↗