Medullary Vasomotor Center Research Articles

Medullary vasomotor center: a modern view of the structure, function and its role in arterial hypertension pathogenesis

The medullary centers of blood pressure regulation have been in the field of vision of both physiologists and doctors for a very long period of time. This is mainly due to the abundance of structures and interstructural interactions in the brain stem, involved in maintaining blood pressure. Advances in research technology open new opportunities these days to look at this problem from a different angle. Moreover, research of medullary centers of blood pressure regulation will make it possible to understand better the mechanisms of persistent increase in blood pressure, which will create the preconditions for the formation of new pathogenetically substantiated therapeutic approaches in the treatment of such a widespread and dangerous pathology as arterial hypertension. Therefore, the aim of this work was to analyze modern views about the structure and composition of the medullary vasomotor center, its functions and its role in the arterial hypertension development. To achieve this goal, the search by keywords: arterial hypertension, baroreflex, NTS, DMN, RVLM, CVLM, CPA, SHR, LC and analysis of scientific articles from the databases of search engines Google Scholar, Web of Science, Pub Med was done. Conclusions: 1. The analysis of literature sources showed that the concept of "medullar vasomotor center" includes a number of brainstem formations, the most studied of which are the structures of the dorsal complex of the vagus nerve (the nucleus of the solitary tract, the dorsal motor nucleus, area postrema), the rostral and caudal ventrolateral regions of medulla, caudal pressor area, noradrenergic structures of the brainstem, in particular the locus coeruleus, as the biggest of them. 2. According to literary sources, arterial hypertension is accompanied by the changes in the morphofunctional state of the above-mentioned structures. The most common mechanisms are violation of the neurotransmitter composition within the structure and the neuroinflammatory process.

Efficacy of clonidine as an adjuvant to bupivacaine for caudal analgesia in children undergoing sub-umbilical surgery

Caudal epidural analgesia with bupivacaine is very popular in paediatric anaesthesia for providing intra- and postoperative analgesia. Several adjuvants have been used to prolong the action of bupivacaine. We evaluated the efficacy of clonidine added to bupivacaine in prolonging the analgesia produced by caudal bupivacaine in children undergoing sub-umbilical surgery. One hundred children, age one to three years, undergoing sub-umbilical surgery, were prospectively randomized to one of two groups: caudal analgesia with 1 ml/kg of 0.25% bupivacaine in normal saline (Group A) or caudal analgesia with 1 ml/kg of 0.25% bupivacaine with 1 µg/kg of clonidine in normal saline (Group B). Post-operative pain was assessed for 24 hours using the FLACC scale. The mean duration of analgesia was significantly longer in Group B (593.4 ± 423.3 min) than in Group A (288.7 ± 259.1 min); P < 0.05. The pain score assessed using FLACC scale was compared between the two groups, and children in Group B had lower pain scores, which was statistically significant. The requirement of rescue medicine was lesser in Group B. Clonidine in a dose of 1 µg/kg added to 0.25% bupivacaine for caudal analgesia, during sub-umbilical surgeries, prolongs the duration of analgesia of bupivacaine, without any side effects.

Study Of Comparative Effects Of Oral Clonidine Vs Oral Diazepam Pre-Medication On The Extent And Duration Of Sensory Blockade In Patients Undergoing Vaginal Hysterectomy Under Spinal Anaesthesia

Clonidine stimulates alpha 2 adrenergic inhibitory neurons in medullary vasomotor centre which decreases sympathetic outflow. Decreased sympathetic nervous system activity is manifested as decreases in systemic blood pressure, heart rate and cardiac output. Our results show that there was significant difference in the time of onset of anaesthesia, which coincides with the study done by Herbhej singh, George, Y .Gaines and Paul .F.White, in which they concluded that oral Clonidine shortened the onset time of tetracaine’s sensory block & prolonged the duration of sensory & motor block. There are more studies, which also show that oral clonidine premedication prolong the sensory as well as motor blockade from Lignocaine & Tetracaine spinal anaesthesia. The antinociceptive effect produced by the orally administered 2adrenergic agonist is mainly caused by direct spinal activation due to spread of the drug via the systemic circulation into the spinal cord. Neuraxial Clonidine inhibits spinal substance P release and nociceptive neuron firing produced by noxious stimuli. Clonidine modifies function of K channels in the CNS causing cell membrane hyperpolarization which decreases anaesthetic requirements.

Aortic depressor nerve unmyelinated fibers in spontaneously hypertensive rats.

The objective of the present study was to compare the morphology of the unmyelinated fibers in the aortic depressor nerves (ADN) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In anesthetized rats, the ADN was identified by its spontaneous activity synchronous with the arterial pulses. Thin sections of the proximal and distal segments of the ADN were analyzed by electron microscopy, and a morphometric study of the unmyelinated fibers and Schwann cells was performed. The proximal segments of WKY and SHR ADN contain an average of 335 +/- 68 and 130 +/- 14 unmyelinated fibers, respectively (P < 0.05), and the distal segments contain an average of 337 +/- 46 and 242 +/- 77 unmyelinated fibers, respectively (P < 0.05). The distribution of the diameters of unmyelinated fibers was unimodal for both strains, with the histogram from the SHR significantly shifted to the left. Because the unmyelinated fibers play a role in the tonic inhibition of the medullary vasomotor centers, especially in the presence of hypertension, the morphological differences observed in the ADN from SHR may account, at least in part, for the blunted baroreflex of SHR.

Central nervous system and the pathogenesis of hypertension. Sites and mechanisms.

A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat.

Regional distribution of vasconstrictor tone in acute spinal rats.

Rats, chronically instrumented with an electromagnetic flow probe around the carotid, superior mesenteric, or renal artery, or the terminal aorta as well as having an arterial and venous catheter, were anesthetized with either and submitted to high spinal cord transection. One hour later, when the rats had recovered consciousness and the arterial pressure had recovered partially, hexamethonium was intravenously injected for ganglionic blockade. Peripheral resistance (arterial pressure/regional flow) was decreased significantly by ganglionic blockade in the carotid and renal areas but not in the superior mesenteric and hindquarter (terminal aortic) areas. This suggests the presence of sizable vasoconstrictor tone to resistance vessels in the carotid and renal areas but not in the superior mesenteric and hindquarter areas in the acute spinal rat. This distribution of vasoconstrictor tone is similar to that in intact conscious rats in the resting state and suggests the possibility that the vasoconstrictor tone for resistance vessels in intact rats is also for the most part generated in the spinal cord. Spinal transection decreased blood flow in all the four regions, suggesting a decrease in cardiac output due to dilation of capacitance vessels. It is possible that, in intact rats at rest, the so-called medullary vasomotor center is sending tonic impulses for the most part to capacitance vessels.

Role of the medullary vasomotor centre in the development of plateau waves

Plateau waves can sometimes be found in various neurosurgical patients with increased intracranial pressure (ICP). In spite of the clinical importance of the waves, the precise mechanism producing them is still obscure. It has been reported that the waves are often accompanied by a reduction of arterial blood pressure (ABP) and suppression of respiration, suggesting a role of the brain stem in their development. In this study, we induced intracranial hypertension in dogs by occluding the neck veins, then stimulated the pressor and depressor areas of the brain stem, observing changes of ICP, ABP, cerebral blood flow (CBF), respiration and heart rate. Stimulation of the brain stem usually caused an increase in the ICP accompanied by variations of the ABP, CBF, respiration and heart rate. These variations were divided into two types: Type I and Type II. Type I which was induced by the stimulation of the pressor area of the brain stem comprised an arterial pressor response, an increase of CBF, hyperventilation and bradycardia. Type II which was caused by stimulation of the depressor area, included declines of the ABP and CBF, respiratory suppression and bradycardia. Of these, variations observed in Type II were similar in many respects to the plateau waves observed in clinical practice. We suggest that the depressor area of the medullary vasomotor centre may play an important role in eliciting the cerebral vasomotor reaction in the development of plateau waves in intracranial hypertension.

Effects of Oral Clonidine on Baroreflex Function in Patients with Essential Hypertension

Clonidine reduces arterial blood pressure and heart rate by actions within the CNS. The mechanism appears to involve a net reduction of sympathetic outflow involving complex actions of clonidine within the anterior and posterior hypothalamus and medulla to permit increased inhibitor nerve traffic from the nucleus tractus solitarius to the medullary vasomotor center, and parallel enhancement of the vagal cardiac reflex. 1 Isaac L Clonidine in the central nervous system: site and mechanism of hypotensive action. J Cardiovasc Pharmacol. 1980; 2 suppl 1 Google Scholar Since the nucleus tractus solitarius receives baroreflex afferent input from both the carotid sinus and aortic arch, clonidine might be expected to modulate baroreflex function, and several reports have indicated that intravenous (IV) clonidine does potentiate this reflex. 2 Korner PI Oliver JR Sleight P Chalmers JP Robinson JS Eur J Pharmacol. 1974; 28 Google Scholar , 3 Korner PI Oliver JR Sleight P Robinson JS Chalmers JP Eur J Pharmacol. 1975; 33 Google Scholar , 4 Sleight P West MJ The effects of clonidine in the baroreflex arc in man. in: Davies DS Reid JL In: Central action of drugs in blood pressure regulation. 291. University Park Press, London1975 Google Scholar We examined the effects of clonidine when given orally for a prolonged period to patients with mild to moderately severe essential hypertension, and we assessed its influence on baroreflex sensitivity for heart rate.

Effects of Oral Clonidine on Baroreflex Function in Patients with Essential Hypertension

Clonidine reduces arterial blood pressure and heart rate by actions within the CNS. The mechanism appears to involve a net reduction of sympathetic outflow involving complex actions of clonidine within the anterior and posterior hypothalamus and medulla to permit increased inhibitor nerve traffic from the nucleus tractus solitarius to the medullary vasomotor center, and parallel enhancement of the vagal cardiac reflex.1 Since the nucleus tractus solitarius receives baroreflex afferent input from both the carotid sinus and aortic arch, clonidine might be expected to modulate baroreflex function, and several reports have indicated that intravenous (IV) clonidine does potentiate this reflex.

Convergence of autonomic, somatic, and vestibular afferent impulses on single units of the medullary vasomotor center of the cat

Responses of vasomotor neurons of the cat medulla to electrical stimulation of the depressor nerve and of mixed nerves of the limbs and to adequate stimulation of the vestibular apparatus were investigated. Evoked unit activity was demonstrated as groups of action potentials followed by inhibition of spontaneous activity. Three types of unit responses to stimulation of the depressor nerve and somatic afferent fibers and changes in unit activity in response to vestibular stimulation are described. The features distinguishing the convergence of afferent impulses on vasomotor neurons are discussed.

Continuous pressure monitoring in experimental obstructive hydrocephalus. II. The origin of undulating ventricular waves and periodic respirations.

Mayer waves and undulating ventricular waves were produced in hydrocephalic and nonhydrocephalic animals. Carotid sinus stimulation resulted in an increase in both wave forms, whereas carotid sinus denervation resulted in their diminution. The reflex pathway involved in the production of the waves constitutes a feedback mechanism between carotid sinus, the peripheral proprioceptor, and medullary vasomotor center. The ventricular fluid pressure wave forms are the intracranial manifestations of passively transmitted changes occurring in the systemic circulation secondary to dysfunction of the brain stem.

On the problem of reactibility of medullary vasomotor centers in initial stages of hypertension.

On the problem of reactibility of medullary vasomotor centers in initial stages of hypertension.

Circulatory effects of interruption and stimulation of cardiac vagal afferents.

AbstractThe influence of the rhythmic activity in cardiac vagal afferents on the circulation was analyzed in chloralose‐anesthetized cats by observing the cardiovascular responses to sudden interruption of this activity and to afferent stimulation of the cardiac nerves. The evoked responses were compared with those produced by “unloading” and stimulation of arterial baroreceptors. — Elimination of the impulse traffic in vagal afferents produced a blood pressure rise, a tachycardia and vasoconstrictions in skeletal muscle, intestine and kidney, indicating a tonic restraint of these afferents on the medullary vasomotor centre. The responses were generally moderate in the presence of normally functioning arterial baroreceptors but were pronounced after elimination of “buffering” influences from these receptors. — Comparisons of the inhibitory influences from vagal cardiac afferents and baroreceptor afferents, respectively, on the vasomotor centre indicated that the former were preferentially directed to neurons controlling the efferent discharge to the heart and the renal vessels. There was no evidence for a particularly strong engagement of the capacitance vessels in reflex patterns mediated through cardiac afferents. — Low frequency afferent stimulation of the cardiac nerves generally induced a profound brady‐cardia, which was probably due to stimulation of fibres not normally tonically active.

Analysis of the central vasomotor effects of (-)-N-(1-phenylethyl)guanidine, a new adrenergic neuron blocking agent.

Central vasomotor effects of (−)-N-(1-phenylethyl)guanidine, a potent adrenergic neuron blocking agent, were studied. The compound was localized in the central sites by intracerebroventricular injection, topical application on the vasomotor center, intra-arterial (vertebral) injection, and intrathecal injection. It potentiated the carotid occlusion response, response to anoxia, spinal compression vasomotor response, and the threshold and optimal vasomotor responses to direct electrical stimulation of the medullary vasomotor center without affecting the peripheral norepinephrine pressor response and the nictitating membrane response. The peak effect was obtained in 15–20 min, and recovery occurred in 80–90 min. The compound probably made catecholamines unavailable to the vasomotor neurons, making them more excitable.

Effect of histamine and antihistaminics on central vasomotor loci

Histamine (50–500 μg) injected into the cerebral ventricles (ICV) produced a pressor response in cats, which was abolished by spinal section and blocked by small doses of mepyramine (100 μg ICV) and tripelennamine (100 μg ICV). Central administration of mepyramine alone produced a depressor response and blocked both reflex as well as direct excitability of the medullary vasomotor centre. On the other hand ICV tripelennamine either had no effect on the blood pressure or elicited a mild pressor response and facilitated the pressor responses to carotid occulsion as well as electrically evoked medullary responses. These results suggest the presence of histaminergic receptors in the central vasomotor loci. However, mepyramine and tripelennamine had divergent effects unrelated to their antihistaminic activity.

Influence of nicotine on intraventricular cerebrospinal fluid pressure in the anaesthetised cat.

Nicotine injected intravenously in small doses (2.5–10.0 μg/kg) produced in anaesthetised cats a rise in cerebrospinal fluid pressure which was probably secondary to an increase in cerebral blood flow. Two possible mechanisms of action are discussed which involve the medullary vasomotor centre and brain stem reticular formation. It is suggested that the response is mediated via a sympathetic cerebral vasodilator pathway.

Role of acetylcholine in central vasomotor regulation.

The present study was undertaken to investigate the role of acetylcholine in central vasomotor regulation in dogs. Both acetylcholine and carbachol produced a pressor response on intracerebroventricular (i.c.v.) administration. This response was completely blocked by pretreatment with i.c.v. atropine. Administration of hemicholinium into the lateral cerebral ventricle as well as its topical application to the floor of the fourth ventricle depressed the responsiveness of the medullary vasomotor center. Furthermore, choline, a precursor of acetylcholine, reversed the effects of hemicholinium. It is concluded that acetylcholine has an excitatory role in the medullary vasomotor center.

A study of the central vasomotor effects of 2-dimethyl aminoethanol (Deanol).

There are a number of observations which suggest that acetylcholine exerts an excitatory influence over the medullary vasomotor center. Dhawan et al. (1) reported that both acetylcholine and carbachol produce a pressor response on intracerebroventricular (i.c.v.) administration in dogs and this pressor response is blocked by atropine. Sinha et al. (2) observed that hemicholinium, which blocks the synthesis of acetylcholine depresses the responsiveness of vasomotor center on i.c.v. administration as well as after topical application to the floor of the fourth ventricle. Release of acetylcholine by tyramine has been suggested to be involved in the pressor response produced by i.c.v. administration of tyramine (1). Pfeiffer et al. (3) studied several compounds to find out longer acting parasympathomimetic agents or precursors of acetylcholine which might affect the central nervous system. They reported parasympathomimetic and central effects of 2-dimethyl aminoethanol (deanol) and suggested that it owes the actions to its conversion to acetylcholine. We, therefore, thought it worthwhile to study the central vasomotor effects of deanol and to investigate if these effects are due to its conversion into acetylcholine.

Changes in electrical activity of the medulla during stimulation of receptors in urinary bladder

1. In experiments on cats under general anesthesia and also in decerebrate preparations both increases and decreases in neural activity in the medulla at the level of the obex were observed in response to stimulation of the mechanoceptors of the urinary bladder. 2. Increased activity arose in the parvocellular, ventral, and lateral reticular nuclei, between them, in the medial structures of the medulla, in the accessory nucleus of the inferior olive and in the adjacent dorsal region, and also (in a few experiments) in the region of the nucleus gracilis, the dorsal nucleus of the vagus and the nucleus of the fasciculus solitarius. Depression was recorded in the inferior olive (in the principal and accessory nuclei), in the ventral and lateral nuclei and in the region between these structures and bounded by them. 3. The close juxtaposition of “points” with facilitation and with depression of electrical activity during stimulation of the mechanoceptors of the bladder gives rise to a mosaic distribution of the zones of excitation and inhibition in the medulla. 4. It may be postulated that the effects observed are the result of changes in the activity of both afferent and efferent bulbar links of the reflex arc connected both with the mechanoceptors of the bladder and the activity of the neurons of the medullary vasomotor center.

The hypothermic effect of pentobarbital in the rat: Sites and mechanisms of action

Summary Systemic administration of pentobarbital to the rat leads to a fall in body temperature. The hypothermia is due to a combination of decreased metabolic heat production and increased heat loss through the skin as a result of peripheral vasodilation. There was no direct correlation between the rate of fall in temperature and the decrease in oxygen consumption. The rate of fall in temperature was determined primarily by the temperature gradient between the animal and the environment. The known effects of pentobarbital in decreasing oxidative processes in the tissues and in blocking transmission in autonomic ganglia could account for these changes. Microinjection of pentobarbital into the hypothalamus and the medullary vasomotor centers was without effect on the core temperature. It is concluded that the fall in temperature during barbiturate anesthesia is not due to a direct effect on the thermoregulatory centers in the hypothalamus.