H. Seller

The localization of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of the afferent input

SummaryIn 78 anaesthetized cats the lower brain stem was explored with microelectrodes for localization of the secondary neurones of the carotid sinus primary afferents. By means of recording single unit activities and evoked potentials (E.P.) by stimulation of the carotid sinus nerve (CSN) these neurones were located exclusively in the nucleus tractus solitarius (NTS) at the level of the obex.The E. P. was recorded with both ipsilateral and contralateral CSN stimulation.During repetitive stimulation of the CSN the frequency transmission across the synapse showed a sharp frequency limitation. With 10 Imp/sec the amplitude of the E.P. was only 50% of the maximal amplitude obtained with 1 Imp/sec. This frequency limitation is also manifested in the frequency effectiveness of the whole baroreceptor reflex measured as blood pressure reduction. It showed a maximum with frequencies of 20–30 Imp/sec, while stimulation of the secondary neurones in the NTS showed an increase in blood pressure reduction up to the tested frequencies of 120 Imp/sec.The E.P. was tested in the different phases of the respiratory cycle. No difference in amplitude or latency between the E.P. was noted.The relevance of these findings to the arrangement of the central neural substrates for the cardiovascular control is discussed.

Interaction of baroreceptor afferents from carotid sinus and aorta at the nucleus tractus solitarii.

SummaryIn chloralose-urethane anaesthetized cats, low-threshold baroreceptor afferents of the carotid sinus and aortic nerves were stimulated electrically. Evoked responses were recorded within the nucleus tractus solitarii near the obex. At a certain electrode position in this area an evoked potential (E. P.) was elicited by stimulation of the homolateral carotid sinus or aortic nerve as well as the contralateral sinus or aortic nerve.At this site an interaction of these four baroreceptor nerves was demonstrated by testing the E. P. of one nerve after a conditioning stimulation of another nerve. Simultaneous E. P.s did not show arithmetical summation. A strong reduction of the test-E.P. (mean value of reduction: 50%) occurred with a conditioning-testing interval of 10–20 msec. The test-E. P. came back to the control amplitude at an interval of 100–150 msec.Neither picrotoxin nor strychnine changed the time course or extent of these interactions.It was further observed that the most effective conditioning-testing interval for inhibition of test response corresponded closely to the difference between the arrival times of arotic and sinus nerve activities evoked by the cardiovascular pulse (aortic 16±5 msec before sinus nerve).

The course of inhibition of sympathetic activity during various patterns of carotid sinus nerve stimulation.

SummaryIn 63 chloralose-urethane anaesthetized dogs both carotid sinus nerves (CSN) and cervical vagal nerves were cut and the sympathetic activity was recorded.During bilateral CSN-stimulation for 2 min the following pattern of sympathetic inhibition was observed:a)A complete inhibition took place after a latency of 181±23 msec. This initial inhibition increased with increasing stimulation frequency up to a maximal tested frequency of 150/sec.b)After this initial inhibition sympathetic activity increased and reached a steady state level. The time required for this adaptation increased up to stimulation frequencies of 30–40/sec and remained constant at 20–30 sec at higher frequencies. Maximal steady state inhibition was obtained with frequencies of 20–30/sec.c)In comparison to CSN stimulation with continuous and interrupted trains the latter reduced the adaptation and was more effective in steady state inhibition of sympathetic activity.

Neuronal activity in the lower brain stem with reference to the circulation

Im unteren Hirnstamm des Hundes wurden extracellulare Mikroableitungen von einzelnen Neuronen durchgefuhrt. Die Beziehungen der abgeleiteten Aktivitat zum Kreislauf wurden untersucht. Die Lage der Ableitpunkte wurde histologisch kontrolliert. Es wurden verschiedene Arten von Zuordnungen der zentralen Aktivitat zum Kreislauf beobachtet: 1. Pulssynchron entladende Neurone. Sie fanden sich fast ausschlieslich in Kerngebieten am Tractus solitarius. In diesem Falle verschwand ihre Aktivitat nach doppelseitiger Vagotomie. Auserhalb dieses Gebietes wurden pulsrhythmische Entladungsmuster nur sehr selten an vereinzelt liegenden Neuronen beobachtet. Sie traten manchmal vorubergehend bei starker arterieller Drucksteigerung auf. Gelegentlich wurden Neurone mit gleitenden Zuordnungen zum Pulsrhythmus abgeleitet. 2. Nicht pulssynchron entladende Neurone, die ihre Entladungsfrequenz bei spontaner oder experimentell erzeugter Anderung des arteriellen Druckes anderten. Sie lagen verstreut in der Formatio reticularis auserhalb der spezifischen End- oder Ursprungskerne. Sie stellten etwa ein Viertel aller abgeleiteten nicht pulssynchronen Neurone dar. Bei experimenteller Blutdrucksteigerung verminderten 38 dieser „Blutdruckabhangigen Neurone“ (B. N.) ihre Entladungsfrequenz, 17 steigerten sie. Bei der Mehrzahl der darauf untersuchten B. N. wurde die Blutdruckabhangigkeit durch Vaguskuhlung allein oder mit zusatzlicher Sinusdenervierung aufgehoben, abgeschwacht oder umgekehrt.SummaryIn the lower brain stem of dogs extracellular microrecordings of single neuron activity were performed. The relationship of the recorded activity to the circulatory system was investigated. The anatomical site of the microelectrode tip was controlled histologically.Different kinds of discharge pattern related to circulatory parameters were observed:1.Discharges synchronous with the cardiac cycle were found nearly exclusively in the region of Nucl. tractus solitarius. They disappeared after bilateral vagotomy. Outside the tractus solitarius region discharges with cardiac rhythm were found very seldom in individual neurons. Sometimes cardiac rhythm arised sporadically during excessive arterial blood pressure increase. A few neurons with sliding coordination to the cardiac rhythm were recorded outside the solitary region.2.Neurons with no cardiac rhythm, exhibiting variations of discharge frequency parallel with spontaneous or experimentally produced variations of blood pressure. They were scattered throughout the reticular formation outside the specific nuclei of the medulla. About one quarter of the recorded neurons without cardiac rhythm reacted to blood pressure variations. During artificial blood pressure rise 38 of these “blood pressure dependent neurons” (b. p. d. n.) diminished, 17 enhanced their activity. Cooling the vagi alone or combined with carotid sinus denervation abolished, diminished or reversed the reaction to blood pressure changes in the majority of the b. p. d. n. tested in this way. Distension of both carotid sinuses by inflatable balloons evoked multiple activity in the immediate rostral neighbourhood of the above mentioned region with cardiac rhythm. Some individual neurons in the reticular formation increased or decreased their discharge frequency during carotid sinus distension.The possible function of the recorded neurons for the cardiovascular control, especially of the b. p. d. n. with no cardiac rhythmicity is discussed. It is stressed that neurons in the lower brain stem which innervate other than the cardiovascular systems could likewise be influenced by arterial pressure changes.ZusammenfassungIm unteren Hirnstamm des Hundes wurden extracelluläre Mikroableitungen von einzelnen Neuronen durchgeführt. Die Beziehungen der abgeleiteten Aktivität zum Kreislauf wurden untersucht. Die Lage der Ableitpunkte wurde histologisch kontrolliert. Es wurden verschiedene Arten von Zuordnungen der zentralen Aktivität zum Kreislauf beobachtet:1.Pulssynchron entladende Neurone. Sie fanden sich fast ausschließlich in Kerngebieten am Tractus solitarius. In diesem Falle verschwand ihre Aktivität nach doppelseitiger Vagotomie. Außerhalb dieses Gebietes wurden pulsrhythmische Entladungsmuster nur sehr selten an vereinzelt liegenden Neuronen beobachtet. Sie traten manchmal vorübergehend bei starker arterieller Drucksteigerung auf. Gelegentlich wurden Neurone mit gleitenden Zuordnungen zum Pulsrhythmus abgeleitet.2.Nicht pulssynchron entladende Neurone, die ihre Entladungsfrequenz bei spontaner oder experimentell erzeugter Änderung des arteriellen Druckes änderten. Sie lagen verstreut in der Formatio reticularis außerhalb der spezifischen End- oder Ursprungskerne. Sie stellten etwa ein Viertel aller abgeleiteten nicht pulssynchronen Neurone dar. Bei experimenteller Blutdrucksteigerung verminderten 38 dieser „Blutdruckabhängigen Neurone“ (B. N.) ihre Entladungsfrequenz, 17 steigerten sie. Bei der Mehrzahl der darauf untersuchten B. N. wurde die Blutdruckabhängigkeit durch Vaguskühlung allein oder mit zusätzlicher Sinusdenervierung aufgehoben, abgeschwächt oder umgekehrt. Bei Dehnung der Carotissinus wurde Aktivitätssteigerung mehrerer benachbarter Einheiten nur dicht rostral der unter 1. beschriebenen Region im Solitarius-Kerngebiet gefunden. Vereinzelt in der Formatio reticularis liegende Neurone steigerten oder senkten ihre Frequenz bei Carotissinusdehnung.Die mögliche funktionelle Rolle der abgeleiteten Neurone im Rahmen der nervösen Kreislaufsteuerung wird diskutiert. Es wird darauf hingewiesen, daß auch in anderen Systemen des unteren Hirnstammes ähnliche Beeinflußungen vom Kreislauf aus möglich sind.

Reduction of renal nerve activity by volume expansion in conscious cats.

SummaryIn conscious cats with intact or denervated baroreceptors volume expansion of 5–15% of blood volume was, performed with dextran and isotonic sodium chloride. Renal sympathetic activity (RSA), electroencephalogram (EEG) blood pressure (BP) and heart rate (HR) were recorded. RSA was reduced by 25–85% in 10 experiments out of 11 by volume expansion both with dextran and isotonic sodium chloride. Reduction of RSA could not be related to different states of wakefulness as indicated by the EFG, so could only be caused by volume expansion, although no quantitative correlation could be detected. No differences were observed between animals with intact and denervated baroreceptors. In most experiments BP and HR decreased during volume expansion up to −25 mm Hg and up to −23 beats/min, respectively. The degree of BP and HR reduction could not be related to the degree of RSA reduction. The results suggest that changes in RSA might be involvec in the renal response to volume expansion.

Über die Abhängigkeit der pressoreceptorischen Hemmung des Sympathicus von der Atemphase und ihre Auswirkung in der Vasomotorik

SummaryThe reflex effects of short bilateral sinus nerve stimulation are dependent on the time of stimulation within the respiratory cycle.Stimulation during the expiratory phase produces greater vasodilatation in the perfused m. gracilis and stronger inhibition of lumbar sympathetic activity than does stimulation during the inspiratory phase. The time course of reflex sympathetic inhibition during the respiratory cycle, measured by the reflex pause of sympathetic activity after sinus nerve stimulation, is described.Continuous stimulation of both sinus nerves intensifies the respiratory grouping of sympathetic activity. This phenomenon can be explained by the respiratory oscillation of reflex transmission.The respiratory grouping of sympathetic activity and the respiratory vasomotor oscillations cannot be abolished by baroreceptor denervation and/or elimination of respiratory movements with neuromuscular blocking agents.If the baroreceptor nerves are intact the respiratory variations are modified also by respiratory blood pressure waves.The significance of the findings with respect to the central functional organization of respiratory and cardiovascular centers and the various factors responsible for the respiratory grouping of sympathetic activity are discussed.ZusammenfassungTestreizung beider Sinusnerven am narkotisierten Hund mit rein depressorisch wirksamen Reizparametern ergibt verschiedene Reizerfolge, abhängig vom Zeitpunkt der Reizung in bezug auf die Atemphase.Exspiratorische Reizung führt zu stärkerer Vasodilation im isoliert durchströmten Muskel und stärkerer Hemmung der Aktivität des lumbalen Sympathicus als inspiratorische. Der Zeitverlauf der pressoreceptorischen Sympathicushemmbarkeit über den gesamten Atemcyclus, gemessen an der Entladungspause im Sympathicus, wird beschrieben.Dauerreizung beider Sinusnerven führt zu verstärkter atemrhythmischer Schwankung der Sympathicusaktivität. Dieses Phänomen wird durch die atemrhythmische Erregbarkeitsschwankung erklärt.Atemsynchrone Schwankungen der Sympathicusaktivität und des peripheren Widerstandes bleiben nach Ausschaltung der Pressoreceptoren und/oder der Atemmechanik bestehen.Bei intakten Pressoreceptoren werden sie auch durch atemsynchrome Blutdruckschwankungen reflektorisch modifiziert.Aus den Befunden werden Schlußfolgerungen auf die funktionelle Organisation des Atem- und Kreislaufzentrums gezogen, sowie auf die bei der Entstehung atemsynchroner Schwankungen der Sympathicusaktivität beteiligten Faktoren.

A descending sympathoinhibitory tract in the ventrolateral column of the cat.

SummaryThe spinal cord at the level of C1 to C2 was explored in chloraloseurethane anaesthetized cats. Lesions and stimulations were performed to localize a sympathoinhibitory tract transmitting the baroreceptor reflex.A. LesionsThe baroreceptor reflex was abolished only when bilateral lesions included extensive parts of the dorsolateral column destroying sympathotonic efferents. The blood-pressure was thereby reduced to a level of 50–60 mm Hg.B. StimulationsIn curarized and atropinized animals the ventral part of the spinal cord was explored by unipolar stimulations with square wave pulses of 1 msec duration and up to 5 V intensity. The ventral part of the spinal cord cranially to the stimulated point was then destroyed by high frequency coagulation. The effects of the stimulation were measured by recording either the blood-pressure or the activity of the renal sympathetic nerve. Stimulation in a region ventrolateral to the ventral horn caused distinct reduction in blood-pressure and inhibition of the sympathetic activity. The effects are believed as indicating an excitation of descending sympathoinhibitory fibers. Their association with different functional systems is discussed.

Influence of intracranial osmotic stimuli on renal nerve activity in anaesthetized cats

SummaryIn baroreceptor denervated cats one internal carotid artery (ICA) or the cerebral ventricular system (CVS) was perfused with isotonic, hypertonic and hypotonic sodium chloride solutions. Renal sympathetic activity (RSA) and blood pressure (BP) were recorded.ICA perfusion with isotonic sodium chloride (150 mM NaCl) produced no changes of RSA compared to control levels. RSA was increased from +30% to +350% in 44 tests out of 45 tests following hypertonic (425 mM NaCl) ICA perfusion. RSA was decreased following hypotonic (aqua dest.) ICA perfusion from −30% to −100% in 37 tests out of 50 tests. The degree of RSA changes was found to depend upon the osmolarity of the solutions. 425 mM NaCl and aqua dest. produced greater RSA changes than 290 mM NaCl and 75 mM NaCl.CVS perfusion with isotonic sodium chloride produced a slight increase of RSA compared to control levels (+15%). Hypertonic sodium chloride produced a RSA increase from +15% to +135% in 10 tests out of 14 tests. Hypotonic sodium chloride produced a RSA decrease from −15% to −80% in 8 tests out of 14 tests.Changes of RSA following ICA perfusions and CVS perfusions were accompanied by changes of BP in the same direction. A quantitative correlation between ΔRSA and ΔBP could not be found.Results suggest that renal osmoregulatory response to osmotic stimuli in the carotid artery may not just arise in response to changing ADH levels but may also be induced by changes in RSA.

Excitation of expiratory neurones adjacent to the nucleus ambiguus by carotid sinus baroreceptor and trigeminal afferents

SummaryExpiratory neurones were recorded in chloralose-urethane anaesthetized cats. Both vagal nerves were cut. After raising the pressure in bilateral carotid sinus preparation the duration and the number of impulses per expiratory cycle increased, while the mean frequency decreased. Since a fall in blood pressure by intravenous acetylcholine resulted in an opposite effect, the described response of expiratory neurones is due to baroreceptor afferents.The expiratory activity was increased even more by trigeminal afferents activated by manual pressure on snout and eyeball.The location of expiratory neurones as controlled histologically, was in a caudal and lateral region of the brain stem adjacent to the nucleus ambiguus. This location and the activation of expiratory neurones by baroreceptor and trigeminal afferents known to cause a strong bradycardia give some further evidence that the nucleus ambiguus represents the origin of vagal cardiomotor efferents and that both the expiratory and vagal activity have a close functional connection.

Zeitliche Eigenschaften der Vasomotorik

SummaryThe resistance to flow was measured with high sensitivity in an isolated skin area of dogs. Constrictions of the vessels were induced by stimulation of the skin nerve.1. The shortest latency measured between a single stimulus and the beginning of the constriction was 230 msec.2. By a single stimulus or by a short burst of stimuli constrictions were induced with a characteristic time course: the increase of resistance varied between 5 and 30% of the control, but the time of increase to maximum value and the time of decrease to the control value were nearly constant in all cases. The increase time was 8–10 sec and the decrease time 30–40 sec. Consequently the steepness of the increase and decrease was a function of the constriction amplitude.3. Three kinds of constriction patterns were observed during continuous constant stimulation: a) Continuous increase of the resistance until a new steady state was reached. This increase could continue over long periods at low stimulation frequencies e. g. more than one hour at one stimulus per second. b) First increase and thereafter decrease of resistance during stimulation. c) Appearance of periodic constrictions and dilatations.4. When the time interval between two single stimuli was varied systematically, the greatest constrictions occurred at stimulus intervals between 20 and 50 msec. At longer or shorter stimulus intervals the resulting constriction decreased down to the effect of one single stimulus.5. The relation between stimulus frequency and constriction amplitude was studied with constant numbers of stimuli. This relation showed a steep increase at low frequencies up to a maximum between 20 and 50/sec and a continuous decrease at higher stimulation frequencies. The curve agrees well with the known results from other vascular areas and with the effects of the double stimuli described under 4.It is suggested that the form of the observed vascular reactions is caused partly by properties of the vascular smooth muscle, partly by the kind of transmitter release from the nerve endings.ZusammenfassungAn einem isolierten, rein constrictorisch reagierenden Hautgefäßgebiet des Hundes wurden die Widerstandsänderungen bei indirekter Reizung hochempfindlich registriert.1. Die kürzeste gemessene Latenzzeit von einem Einzelreiz bis zum Beginn der Constriction lag bei 230 msec.2. Durch Einzelreize oder Reizserien, die kurz gegenüber der Constrictionszeit waren, wurden vorübergehende Widerstandszunahmen mit einem charakteristischen Zeitverlauf ausgelöst. Bei Widerstandsänderungen zwischen 5 und 30% des Ausgangswertes war der Gesamtzeitverlauf unabhängig von der Constrictionsgröße, die Anstiegszeit betrug 8–10 sec, die Abfallzeit 30–40 sec. Nur die Steilheit der Verläufe war eine Funktion der Constrictionsgröße.3. Konstante Dauerreizung ergab unterschiedliche Verlaufsformen des Gefäßwiderstandes: a) Fortwährende Zunahme des Widerstandes unter der Reizung bis auf einen neuen Gleichgewichtszustand, der auch schon bei Reizfrequenzen von 0,5–1/sec hohe Werte erreichte. b) Zunahme und Wiederabnahme des Widerstandes unter der Reizung. c) Auftreten rhythmischer Constrictionen.4. Reizung mit Doppelreizen in unterschiedlichen Abständen ergab maximale Reizerfolge bei Abständen von 20–50 msec. Sowohl bei weiterer Verlängerung als auch Verkürzung des Reizabstandes gegenüber diesen Zeiten ging der Erfolg des Doppelreizes zurück, bis er den eines Einzelreizes erreichte.5. Die Reizfrequenz-Effekt-Charakteristik wurde bei konstanten Reizzahlen ermittelt. Mit steilem Anstieg bei niedrigen Frequenzen zu einem Maximum zwischen 20 und 50/sec und Wiederabfall bei höheren Frequenzen stimmt sie grundsätzlich mit dem bekannten Verhalten anderer Gefäßgebiete überein, ebenso mit den Ergebnissen der Doppelreizungen.Als Ursachen für die beobachteten Verläufe werden zum Teil Eigenschaften der Gefäßmuskulatur, zum anderen solche der Erregungsübertragung diskutiert.