Proceedings: Baroreceptor reflex inhibition of a spinal sympathetic reflex.
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Biomedical subjects
Publications and source records attributed to J H Coote.
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1. In anaesthetized cats the effects were investigated of electrical stimulation of regions in the caudal mesencephalon, pons and medulla on muscle blood flow, skin blood flow and arterial blood pressure.2. It was found that within the dorsal part of the well known pressor area there is a narrow strip, 2.5 mm lateral from the mid line, starting ventral to the inferior colliculus and ending in the medulla close to the floor of the IV ventricle, from which vasodilatation in skeletal muscles is selectively obtained. This strip is quite separate from the more ventral, efferent pathway for active vasodilatation running from the hypothalamic and rostral mesencephalic ;defence centre'.3. As in the case of the hypothalamic and rostral mesencephalic ;defence centre', the muscle vasodilatation obtained from the caudal strip is accompanied not only by a rise of arterial blood pressure, but also by tachycardia, vasoconstriction in the skin, pupillary dilatation and piloerection.4. Stimulation, restricted to the caudal strip, via implanted electrodes in unanaesthetized animals, produced a behavioural response resembling the defence reaction. The strip, therefore, is probably a caudal extension of the ;defence centre'.5. Unlike the vasodilatation elicited from the more rostral part of the ;defence centre' in the hypothalamus and mesencephalon, the muscle vasodilatation obtained on stimulation of the caudal strip was resistant to atropine, but was blocked by guanethidine.6. It is suggested that during naturally occurring defence reactions in the normal animal the ponto-medullary area is activated together with the hypothalamo-mesencephalic area, inhibition of vasoconstrictor tone then accompanying activation of the vasodilator nerve fibres in skeletal muscle.
1. In decerebrate cats, passive movements of one hind limb led to increases in arterial blood pressure, heart rate and ventilation. When both limbs were moved the magnitude of the changes was approximately doubled.2. Section of the nerves to the limb abolished the responses to movement. The responses are, therefore, dependent on a reflex originating in the moving limb.3. The magnitude of the cardiovascular responses was significantly reduced following section of the sensory nerve fibres from the knee joint, in an otherwise partially denervated limb. This indicates that part of the reflex changes associated with limb movement arise from sensory endings in the joints.4. Electrical stimulation of articular nerves led to similar cardiovascular responses. The afferent fibres involved were identified as those having conduction velocities below 18 m/sec, whose terminations are classified as the type IV joint receptors. The possibility that these subserve some other function than pain is discussed.
1. The effect of electrical stimulation of the distal cut ends of the renal nerves of unilaterally nephrectomized, anaesthetized cats was studied. Using stimulation parameters of 15 pulses per second (pps), 15 V and 0.2 msec duration, there was an immediate sharp drop in renal blood flow, as determined by an electromagnetic flowmeter, which was maintained for about 2 min. Flow gradually returned to control values over approximately the next 10 min in spite of continued stimulation for up to 30 min.2. Plasma renin activity (PRA) increased markedly after 10 min of stimulation but 20 min later fell towards pre-stimulation values whether stimulation was maintained or not.3. Phentolamine, an alpha-adrenergic-receptor antagonist, abolished both the blood flow and PRA responses to a 10 min period of renal nerve stimulation.4. When the renal artery was constricted in order to produce blood flow changes similar to those found with renal nerve stimulation, the rise in PRA was similar to that observed with renal stimulation.5. In phentolamine-blocked animals, renal artery constriction, as described, produced the same effect on PRA as was observed with renal nerve stimulation.6. Propranolol, a beta-adrenergic-receptor antagonist, did not block the blood flow response to renal nerve stimulation, but did block the rise in PRA normally associated with renal nerve stimulation.7. It is suggested that the effect of renal nerve stimulation on PRA is mediated, primarily, by changes in renal blood flow and that one of the steps leading to renin release following stimulation is sensitive to propranolol. This step must be distal to the effect on vascular smooth muscle.
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1. In anaesthetized cats tetanic contraction of the hind-limb muscles, elicited by stimulating the ventral roots L6-S1, caused a rise of arterial blood pressure, usually accompanied by small increases in heart rate and pulmonary ventilation: in decerebrate cats, all components of the response were much increased.2. With tetani of different strengths, obtained by stimulating with different intensities at the same frequency, the pressor response increased with increasing tension.3. When muscle contraction had been abolished by gallamine, or when dorsal roots L6-S1 had been sectioned, ventral root stimulation no longer caused a pressor response. The response is therefore a reflex, initiated in the exercising limb.4. The pressor response was not affected by section of all articular nerves to knee and ankle joints, or by section of the vagi. The stimulus therefore originates in the contracting muscles alone.5. The pressor response is potentiated by occluding the circulation through the working muscles. Reasons are discussed for concluding that the stimulus is chemical rather than mechanical, and that the ;metabolic receptors' for this exercise reflex are the free endings of group III and IV sensory nerve fibres located around the blood vessels.
1. Responses of sympathetic neurones to various afferent inputs have been analysed both in anaesthetized cats with intact neuraxis and in spinal cats.2. In anaesthetized cats electrical stimulation of low threshold group III afferent fibres in skin and muscle nerves inhibited sympathetic neurones and gave depressor responses. The silent period following a sympathetic reflex discharge is most likely due to inhibition brought on by a particular subgroup within this afferent group.3. High threshold group III and group IV afferent fibres excited sympathetic neurones and elicited pressor responses.4. Sympathetic reflex arcs could be temporally facilitated during the somatic afferent induced inhibition, by group IV, and to a lesser extent by group III volleys.5. Section of the spinal cord shortened the time course and lessened the degree of group III inhibition suggesting that suprasegmental pathways are involved in the long-lasting depression following a reflex.6. Baroreceptor afferent stimulation inhibited group III- and group IV- evoked reflexes even with some temporal facilitation in the pathway.7. The special properties of the sympathetic reflex arcs and the relation of the results to other work on B.P. reflexes are discussed. It is suggested that the group III and IV muscle afferents have a chemoreceptor function and are responsible for mediation of the pressor reflex during muscle exercise.
1. Reflex discharges in white rami (WR) were elicited by single-shock stimulation of dorsal roots (DR), splanchnic (SPL) and intercostal nerves (IC).2. The reflexes have been compared in anaesthetized cats with intact neuraxis, after mid-brain transection and after high cord transection. The brain stem can maintain moderate inhibition of the WR responses, but strong inhibition of IC responses. After cord transection all reflexes are released again.3. Stimulation of ventromedial medullary reticular substance could completely, and independently, inhibit maximal SPL-to-WR and IC-to-WR reflexes.4. Carotid sinus distension did not reduce WR responses, indicating that the major part of the volley is not in vasoconstrictor fibres.5. Central delay of DR-to-WR responses is longer than delay of DR-to-IC responses and is unchanged by transections of the neuraxis at mid-brain or high spinal levels.6. There was no facilitation of WR responses by a prior conditioning volley in the visceral or somatic afferent pathway in contrast to early facilitation of the IC responses.
1. In anaesthetized cats distension of carotid sinus inhibited renal nerve activity and intercostal-renal nerve reflexes. The degree of inhibition was dependent on the amount of rise in sinus pressure. Intercostal-intercostal reflexes were not inhibited.2. Inhibition of renal nerve activity and intercostal-renal nerve reflexes could be obtained on stimulating in the dorsal reticular formation but mainly in the ventromedial reticular formation at the level of the obex. The intercostal reflex could also be inhibited at several of these points.3. The possibility that two inhibitory mechanisms are available is suggested, at least one projecting on to spinal reflex arcs.4. Other ways of inhibiting renal nerve activity were shown. One was similar to that produced by single shocks to peripheral skin and muscle nerves, and the other was due to a subnormal excitability of vasomotor neurones following intense activation.
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1. Electrical stimulation of spinal sensory nerves evoked discharges in inferior cardiac and renal nerves. In the anaesthetized cat both an early and a late response could be recorded in each nerve.2. For any one afferent input the central delay of the late cardiac nerve response was significantly less than that of the late renal nerve response. The central delay of the early responses was similar for both nerves. In the spinal cat only the early response was present.3. Cooling the floor of the 4th ventricle abolished the late responses in renal nerves, but left reflex volleys in white rami and intercostal nerves unchanged.4. Stimulation in the brain stem evoked responses in both cardiac and renal nerves which had a shorter latency than the reflexes evoked in these nerves by stimulating dorsal roots.5. The late responses could be abolished by lesions in the cervical spinal cord.6. Such evidence led to the conclusion that there are two pathways for reflex discharge into inferior cardiac and renal nerves, one involving a supraspinal relay and the other confined to the spinal cord.
The aim of this study was to determine the site in the CNS at which 5-hydroxytryptamine (5-HT) inhibits efferent sympathetic nerve activity in the cat. 5-Hydroxytryptamine (3 and 10 micrograms/kg), given into the lateral cerebral ventricle, produced immediate non dose related increases in mean blood pressure (MBP), heart rate (HR) and renal nerve activity (RNA). Larger doses (30 and 100 micrograms/kg i.c.v.) produced gradual decreases in blood pressure, heart rate and renal nerve activity, which did not occur when access of the drug to the fourth ventricle was prevented. Administration of 5-HT (10 and 30 micrograms/kg) into the fourth ventricle produced only decreases in blood pressure, heart rate and renal nerve activity after 15-40 min, which were accompanied by decreases in cardiac output and renal vascular resistance, but little or no change in total peripheral resistance. Application of 5-HT onto the ventral surface of the medulla, into the subarachnoid space at various levels along the spinal cord or into various parts of the nucleus tractus solitarius produced no effect on blood pressure heart rate or renal nerve activity. However, application of a cotton wool pledget soaked in a 5-HT solution (3 mg/ml) over the entire obex/NTS region produced immediate decreases in blood pressure, heart rate and renal nerve activity. These studies suggest that the sympatho-inhibitory effect of 5-HT is due to an action at a site near the caudal end of the dorsal surface of the medulla.
Recent evidence is showing that the paraventricular nucleus (PVN) of the hypothalamus plays a key role in autonomic regulation. Studies by the author of the PVN neurones that project to the spinal cord are reviewed. These neurones are inhibited by arterial baroreceptors and excited or inhibited by pulmonary/cardiac vagal afferents. Volume load or low dose atrionatriuretic peptide can stimulate vagal afferents to excite PVN-spinal neurones. Ibotenic acid-induced lesions of PVN-spinal neurones abolish a reflex increase in renal vascular conductance following volume load. This effect appears to be independent of the PVN-vasopressin or oxytocin-containing neurones which directly excite spinal sympathetic neurones. It is suggested that different chemically coded PVN-spinal neurones produce differential effects on spinal cardiovascular neurones, either monosynaptically or via interneurones.