Spontaneous Sympathetic Activity Research Articles

Evidence for GABA mediation of sympathetic inhibition evoked from midline medullary depressor sites

GABA antagonists blocked, and diazepam potentiated, inhibition of spontaneous sympathetic activity elicited by electrical stimulation of classic midline medullary depressor sites. Picrotoxin often converted inhibitory effects of raphe stimulation into sympathoexcitatory responses. Serotonin antagonists blocked these sympathoexcitatory responses. The midline medullary raphe complex is heterogeneous in respect to autonomic function with sympathoinhibitory elements mediated at least in part by GABA and sympathoexcitatory pathways mediated by serotonin.

DEPRESSION OF NOCICEPTIVE SYMPATHETIC REFLEXES BY THE INTRATHECAL ADMINISTRATION OF MIDAZOLAM

The effect of the intrathecal administration of midazolam 0.5-1.0 mg in 1-2 ml of physiological saline solution, has been observed on responses evoked in renal sympathetic nerves by supramaximal electrical stimulation of radial and tibial nerves. In artificially ventilated dogs anaesthetized with alpha-chloralose, the intrathecal administration of midazolam caused a marked depression of reflexes evoked from the tibial nerve but had no effect on either spontaneous sympathetic activity or reflexes evoked by radial nerve stimulation. Neither the small amount (1-2 microliters) of benzyl alcohol, present as a preservative (administered intrathecally), nor midazolam 1 mg kg-1 i.v. caused any significant depression of the evoked somato--sympathetic reflexes. The effects of intrathecal midazolam were reversed by the benzodiazepine antagonists Ro 15-1788 1 mg kg-1 i.v. and Ro 15-3505 1-2 mg kg-1 i.v. but not by naloxone 2 mg i.v. It is suggested that the antinociceptive effect of locally applied midazolam could be the result of a non-opioid GABA-mediated system which may have implications in the management of pain.

Neuromuscular blocking agents and spontaneous sympathetic activity.

The action of neuromuscular blocking agents on the spontaneous sympathetic activity has been quantitated. "On line" spectrum analysis has been applied to the action potential of pre- and post ganglionic nerves of the coeliac plexus. The activity, the frequency spectrum and their changes after the injection of clinical and high doses of decamethonium, D-tubocurarine, succinylcholine, gallamine and pancuronium are determined.

Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions

The functional consequences of drug-induced stimulation under in vivo conditions of alpha-adrenoceptors and dopamine receptors at vascular adrenergic nerve endings (presynaptic receptors) was studied in the autoperfused hindquarters or hindlegs of cats anaesthetized with urethane. The changes in perfusion pressure in response to electrical stimulation of the lumbar sympathetic chain were taken as a measure of noradrenaline release from the vascular adrenergic nerves. Presynaptic inhibitory alpha-adrenoceptors and dopamine receptors were activated by clonidine and dopamine, respectively. According to in vitro experiments these two drugs are more potent stimulants of peripheral presynaptic than postsynaptic receptors. The lowest frequency of stimulation of the lumbar sympathetic chain which yielded a reproducible pressor response was 4 HZ for the autoperfused hindquarters and 1 HZ for the hindlegs; Clonidine was tested over a wide dose range (1-100 mug/kg i;v). A reduction of the stimulation-induced pressor response in the autoperfused hindquarters or hindlegs was observed only after the rather high dose of 100 mug/kg of clonidine. The inhibition was marked at low frequencies of stimulation (1-4 HZ) and weak or absent at high frequencies (16 and 32 HZ). The dose of clonidine (100 mug/kg) which proved to be effective at presynaptic receptors produced a transient increase in blood pressure and in perfusion pressure of the hindquarters and hindlegs and virtually abolished spontaneous sympathetic nervous activity. In spinal cats, the clonidine-induced increases in blood pressure and perfusion pressure were very pronounced and of rather long duration. Thus, under in vivo conditions clonidine showed no selectivity for presynaptic alpha-adrenoceptors in a blood-perfused vascular bed, and its presynaptic action was negligible as compared to its powerful central sympatho-inhibitory effect. Dopamine was constantly infused into the auto-perfused hindquarters or hindlegs at increasing rates until a vasoconstriction due to stimulation of vascular (postsynaptic) alpha-adrenoceptors occurred. The monoamine did not inhibit the stimulation-induced increases in perfusion pressure of the autoperfused hindquarters or hindlegs and, thus, an effect on presynaptic receptors was not found. The results underscore the importance of in vivo experiments for assessing the therapeutic significance of drug-induced stimulation of presynaptic receptors.

Autonomic complications in a case of severe tetanus

Severe tetanus developed in an elderly white man and he was treated with tracheostomy, therapeutic paralysis with curare and intermittent positive pressure ventilation. Over the initial few days, labile hypertension and tachycardia developed, which were eventually controlled with a trimetaphan infusion and intravenous propranolol. These drugs were withdrawn when profound hypotension developed, and over the next 5 days frequent physical stimulation was necessary to maintain an adequate level of cardiovascular activity. At this time the patient appeared comatose, his muscle tone was flaccid, and there was a marked similarity between the levels of cardiovascular and electroencephalographic activity. The end of the period was marked by a spontaneous increase in electroencephalographic activity and a better maintained blood pressure. Over the next 2 days, muscle spasms and hypertension reappeared, body temperature increased and consciousness returned. Eventual recovery was complete but delayed by a prostatic operation. It appears that in some elderly patients with severe tetanus a transient phase of sympathetic overactivity is followed by a phase when spontaneous sympathetic activity is minimal. During this second phase, massive sympathetic activation can be evoked by various stimuli provided drug-induced depression is avoided.

Further similarities between the action of clonidine and a central activation of the depressor baroreceptor reflex.

The relationship between the central action of the hypotensive drug clonidine and the depressor baroreceptor reflex was studied in cats anaesthetized with urethane. Activation of the depressor baroreceptor reflex was achieved by bilateral electrical stimulation of the sinus nerves. The magnitude of the activation of the reflex was estimated from the resultant decrease in spontaneous sympathetic activity recorded from the preganglionic splanchnic and a postganglionic renal nerve and from the subsequent fall in blood pressure. The effect of bilateral sinus nerve stimulation was frequency-dependent over the range of 2 to 32 shocks/sec and allowed the construction of frequency-response curves. Clonidine in low doses (1 and 3 μg/kg i.v.), which caused no or only a slight depression of spontaneous sympathetic nerve activity and of the blood pressure, increased the response to bilateral sinus nerve stimulation with a resultant shift of the respective frequency-response curves to lower rates of stimulation. Clonidine also augmented the bradycardia produced by an activation of the depressor baroreceptor reflex. These results indicate a facilitation of the depressor baroreceptor reflex by clonidine.

The effect of baroreceptors on the latency of evoked responses in sympathetic nerves during the cardiac cycle.

1. A rapid increase in pressure in a vascularly isolated perfused carotid sinus has been shown to inhibit a reflex response in efferent sympathetic nerves of the dog evoked by electrical stimulation of the radial nerve.2. In intact preparations with the carotid baroreceptors innervated, the mean latency and the variance of the latency of reflex sympathetic nerve responses was reduced when the stimuli evoking the responses were applied at one point of both cardiac and respiratory cycles. When the baroreceptors were denervated there were no significant differences in the responses to random and synchronized stimuli.3. In intact preparations the latency of evoked responses in sympathetic nerves was found to vary progressively during a cardiac cycle; the maximum increase in latency was observed with the responses that occurred at that phase of the cardiac cycle when the baroreceptors exert maximal inhibition on spontaneous sympathetic activity. After denervation of the carotid sinuses a much smaller change during the cardiac cycle was still present, possibly due to effects produced by baroreceptors of the aortic arch and elsewhere.4. It was concluded that changes in baroreceptor activity, due to beat to beat fluctuations of the systemic arterial pressure are a major factor causing variations in the latency of responses in sympathetic nerves evoked by stimuli applied to a cutaneous nerve.

The effects of d-tubocurarine on spontaneous postganglionic sympathetic activity and histamine release.

The effects of d-tubocurarine on spontaneous postganglionic sympathetic activity and histamine release.

Spontaneous sympathetic activity in experimental heart-failure.

Es wird bestatigt, dass der Katecholamingehalt des Herzmuskels bei Herzinsuffizienz abnimmt; ein kompensatorischer Anstieg der Reflexaktivitat des sympathischen Nervensystems besteht hingegen nicht.

Hypothalamic stimulation and the inhibition of the activity of cardiac sympathetic and parasympathetic nerves.

AbstractThe electrical activity from the left sympathetic and parasympathetic cardiac nerves was recorded simultaneously with the activity from bulbar neurones. Electrodes for stimulating or recording were placed stereotaxically in the posterior hypothalamus, in the medulla and in the sygmoid gyrus of a dog.During the hypothalamic stimulation the sympathetic discharge increased but it was strongly reduced immediately after the cessation of the stimuli. In all experiments the spontaneous sympathetic activity was invariably reduced after the hypothalamic stimulation. In most experiments the parasympathetic discharge was also reduced but in some cases the vagal activity was increased simultaneously with the reduction in sympathetic discharge.The reduction in both sympathetic and parasympathetic discharges appeared independently of the values in systemic blood pressure.Several experimental observations indicate that the reduction in the sympathetic activity can not be attributed to fatigue but rather to an ac...