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Biomedical subjects

J H Coote

Publications and source records attributed to J H Coote.

At least 19 recordsLinked to original sources
PubMed2006

Paraventricular nucleus influence on renal sympathetic activity in vasopressin gene-deleted rats.

In Wistar rats, an increase in renal sympathetic activity is induced by activation of presympathetic neurones in the paraventricular nucleus (PVN) and reflexly by a mild venous haemorrhage. Both stimuli are dependent on the release of vasopressin and glutamate at spinal synapses. The significance of the supraspinal pathway and the co-operative interaction of vasopressin with an excitatory amino acid is unclear. The present study examines this in Brattleboro rats, which have a natural vasopressin gene deletion. The responses were compared with Long-Evans rats, from which Brattleboro rats are derived. All rats were anaesthetized with a mixture of urethane (650 mg kg(-1) i.v.) and chloralose (50 mg kg(-1) i.v.). Recordings were made of blood pressure, heart rate and renal sympathetic nerve activity (RSNA). Microinjection of d,l-homocysteic acid (DLH, 0.2 m, 100 nl) at sites restricted to the PVN elicited significant increases in RSNA (P < 0.001) in both strains of rats. These changes were significantly reduced (P < 0.01) in Long-Evans rats by intrathecal application to the spinal cord of either a V(1a) antagonist or a glutamate antagonist (kynurenic acid), whereas in Brattleboro rats the changes were significantly reduced (P < 0.05) only by kynurenic acid. Removal of 1 ml of venous blood in Long-Evans rats increased RSNA by 28 +/- 4% (P < 0.01), which was significantly reduced (P < 0.05) by prior intrathecal application of either the V(1a) antagonist or by kynurenic acid. The same test in Brattleboro rats caused a significantly greater (P < 0.05) increase (63 +/- 14.7%) in RSNA which, in contrast to Long-Evans rats, was unchanged by intrathecal application of the V(1a) antagonist, being significantly reduced (P < 0.01) only by intrathecal kynurenic acid. Thus, in Brattleboro rats, the lack of vasopressin in the brain sympathetic pathways appears to be compensated, acutely, by glutamate-releasing pathways. This might indicate that, in normal rats, vasopressin is more important in maintaining longer term adjustments to stressors.

Animals↗
PubMed2006

The role of supraspinal vasopressin and glutamate neurones in an increase in renal sympathetic activity in response to mild haemorrhage in the rat.

This study investigated the importance of supraspinal vasopressin and glutamate neurones in regulating renal sympathetic activity as part of the response to an acute reduction in blood volume. Wistar rats anaesthetized with chloralose and urethane were instrumented to record arterial blood pressure, heart rate and left renal sympathetic nerve activity. Pharmacological agonists and antagonists to glutamate and vasopressin were applied to the renal outflow of the spinal cord via an intrathecal catheter inserted at the foramen magnum and with the tip at the level of T10. Both glutamate and vasopressin increased renal sympathetic activity, and these actions were shown to be selectively blocked by their respective antagonists. Removing 1 ml of venous blood from a femoral venous catheter elicited an increase of 26 +/- 2% in renal sympathetic activity. This response to mild haemorrhage was halved to 13 +/- 4% by prior intrathecal application of a selective V1a antagonist. Similarly, prior intrathecal application of kynurenic acid reduced the response to the mild haemorrhage from 28 +/- 2 to 12.6 +/- 2.8%. Intrathecal application of both antagonists together reduced the haemorrhage response even further to 8 +/- 3%. All the changes were statistically significant at P < 0.01. It is concluded that a small reduction in blood volume induces an increase in renal sympathetic activity dependent on vasopressin and glutamate release from terminals of supraspinal neurones. It is suggested that the vasopressin neurones most probably originate from the paraventricular nucleus of the hypothalamus.

Adaptation, Physiological↗
PubMed2006

Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats.

In anaesthetised male rats an intravenous (i.v.) injection of p-chloroamphetamine (PCA) produced a specific patterned bursting response in the sympathetic vas deferens nerve (VDN) that corresponds to ejaculation. In the present, study selective dopamine agonists and antagonists were used to investigate whether dopaminergic mechanisms influence the generation of this ejaculatory-related response. Administration of a mixed D(1/2) receptor agonist (0.1-1.0 mg kg(-1) apomorphine i.v.) also evoked the characteristic bursting pattern responses in the VDN. Similar, but fewer, burst pattern responses could also be evoked by a selective D(2/3) receptor agonist (0.1-2.0 mg kg(-1) piribedil). Responses to 1.0 mg kg(-1) apomorphine were blocked by pretreatments with either 0.5 mg kg(-1) remoxipride (D(2) receptor antagonist) or 0.5 mg kg(-1) nafadotride (D(3) receptor antagonist), suggesting that D(2)-like receptors were involved. Responses could not be evoked by i.v. injections of apomorphine (1.0 mg kg(-1)) in anaesthetised male rats with a midthoracic spinal section, indicating that activation of D(2)-like receptors at supraspinal sites leads to an increase in the excitability of the lumbosacral pattern generator for ejaculation. In anaesthetised female rats a similar patterned bursting response occurred in the uterine nerve (UN) in response to apomorphine (0.5-2.0 mg kg(-1) i.v.). Thus a common neural mechanism may regulate sexual climactic reflexes in both sexes.

Anesthesia↗
PubMed2006

Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in anaesthetized male rats.

In urethane-anesthetized male rats, a branch of the hypogastric nerve was shown, anatomically and electrophysiologically, to supply the vas deferens. Recordings from this nerve revealed a low level of tonic activity, which was predominantly efferent motor activity. Administration of p-chloroamphetamine i.v., elicited a rhythmic burst of neuronal activity, coherent with rhythmic pressure increases in the vas deferens and contractions of the bulbospongiosus muscles, which together comprise ejaculation. This response to p-chloroamphetamine was still present after complete transection of the spinal cord at T8-T9. These data indicate that p-chloroamphetamine is capable of activating the spinal neuronal circuits that generate the pattern of autonomic and somatic responses similar to those of sexual climax. Furthermore based on the best documented action of p-chloroamphetamine, the results suggest that the excitability of the pattern generator is regulated by serotonergic, dopaminergic or noradrenergic receptors in the lumbosacral spinal cord. We conclude this animal model will enable robust studies of the pharmacology and physiology of central neural mechanisms involved in ejaculation and sexual climax.

Action Potentials↗
PubMed2006

Sympathetic genital responses induced by p-chloroamphetamine in anaesthetized female rats.

In urethane-anesthetized female rats, a branch of the hypogastric nerve equivalent to the vas deferens nerve in males was shown anatomically and electrophysiologically to supply the uterine horns and we have consequently termed this the uterine nerve. Administration of p-chloroamphetamine i.v. elicited patterned bursting uterine nerve activity responses together with contractions of the uterine horns and musculature of the vaginal wall. These responses are qualitatively similar to ejaculatory responses observed following p-chloroamphetamine administration to anesthetized male rats and the urethrogenital reflex in females, suggesting they represent responses occurring during sexual processes. This response to p-chloroamphetamine was still present after complete transection of the spinal cord at T8. These data indicate that common neurophysiological and pharmacological mechanisms regulate genital reflexes at the lumbosacral spinal level in both the female and the male rat.

Anesthesia↗
PubMed2005

The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans.

We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP). We proposed that PS selectively inhibits cardiac vagal activity. We attempted to test this by performing PS during experimental alterations in vagal tone. Large decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic exercise. Milder alterations in vagal tone were achieved by altering carotid baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps surae was tested in 14 healthy human volunteers. BP, ECG and respiration were recorded. PS alone caused a significant decrease (P < 0.05) in R-R interval (962 +/- 76 ms at baseline compared to 846 +/- 151 ms with PS), and showed a reduction in HR variability, which was not significant. The decrease in R-R interval with PS was significantly less (P < 0.05, n = 3) following administration of glycopyrrolate (-8.1 +/- 4.5 ms) compared to PS alone (-54 +/- 11 ms), and also with PS during handgrip (+10 +/- 10 ms) compared with PS alone (-74 +/- 15 ms) (P < 0.05, n = 5). Milder reductions in vagal activity (NP) resulted in a small but insignificant further decrease in R-R interval in response to PS (-107 +/- 17 ms compared to PS alone -96 +/- 13 ms, n = 5). Mild increases in vagal activity (NS) during PS resulted in smaller decreases in R-R interval (-39 +/- 5.5 ms) compared to PS alone (-86 +/- 17 ms) (P < 0.05, n = 8). BP was not significantly changed by stretch in any tests. The results indicate that amongst muscle receptors there is a specific group activated by stretch that selectively inhibit cardiac vagal tone to produce tachycardia.

Adult↗
PubMed2005

Cardiac vagal tone, exercise performance and the effect of respiratory training.

Heart rate variability (HRV) at rest and heart rate recovery after exercise reflect cardiac vagal activity. The aim of this study was to determine whether increasing HRV during involuntary respiratory training induced by rebreathing air using a Hepburn heart and lung exerciser (HHALE) could, like exercise, improve vagal tone. Eighteen subjects (36-88 years) underwent a 6-week control period, then a 6-week training period with the HHALE following which half continued training for 6 weeks and half ceased training. Measurements were made of HRV, work at 60% predicted heart rate max for 15 min, heart rate recovery after exercise, resting blood pressure, heart rate, vital capacity and forced expiratory volume. After the first 6-week HHALE training, there was a significant increase of 13.2 +/- 5.7 nu in the high frequency peak of the power spectrum of HRV at rest, whereas, the low frequency peak decreased. Similarly, exercise performance showed a significant improvement of 0.031 +/- 0.012 J per heartbeat from a pre-training 0.128 +/- 0.022. Also, heart rate recovery after exercise significantly faster (drop in the first 20 s improving by 3.3 +/- 1.5 beats from a pre-training 12.9 +/- 1.6). The subgroup that continued training maintained or slightly improved these values. In those that ceased training the speed of heart rate recovery at the end of the exercise test returned to pre-trained levels, whereas, other responses were either maintained or decreased slightly. We conclude that training with the HHALE can, without additional exercise, increase cardiac vagal tone and exercise performance.

Adaptation, Physiological↗
PubMed2004

A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney.

It is now well accepted that the sympathetic nervous system responds to specific afferent stimuli in a unique non-uniform fashion. The means by which the brain transforms the signals from a single type of receptor into an appropriate differential sympathetic output is discussed in this brief review. The detection of and response to venous filling are used for illustration. An expansion of blood volume has been shown in a number of species to increase heart rate reflexly via sympathetic nerves and this effect is primarily an action of volume receptors at the venous-atrial junctions of the heart. Stimulation of these volume receptors also leads to an inhibition of renal sympathetic nerve activity. Thus the reflex response to an increase in plasma volume consists of a distinctive unique pattern of sympathetic activity to maintain fluid balance. This reflex is dependent on neurones in the paraventricular nucleus (PVN). Neurones in the PVN show early gene activation on stimulation of atrial receptors, and a similar differential pattern of cardiac sympathetic excitation and renal inhibition can be evoked by activating PVN neurones. Cardiac atrial afferents selectively cause a PVN GABA neurone-induced inhibition within the PVN of PVN spinally projecting vasopressin-containing neurones that project to renal sympathetic neurones. A lesion of these spinally projecting neurones abolishes the reflex. With regard to the cardiac sympathetics, there is a population of PVN spinally projecting neurones that selectively increase heart rate by the release of oxytocin, a peptide pathway that has no action on renal sympathetic outflow. In heart failure the atrial reflex becomes blunted, and evidence is emerging that there is a downregulation of nitric oxide synthesis and reduced GABA activity in the PVN. How this might give rise to increased sympathetic activity associated with heart failure is briefly discussed.

Animals↗
PubMed2004

Effect of hypothermia on baroreflex control of heart rate and renal sympathetic nerve activity in anaesthetized rats.

The present study investigated the effect of acute hypothermia on baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) by generating baroreflex logistic function curves, using bolus doses of phenylephrine and sodium nitroprusside, in anaesthetized male Wistar rats at a core temperature (T(b)) of 37 degrees C, during acute severe hypothermia at T(b)= 25 degrees C and on rewarming to 37 degrees C. Comparisons were made between rats without (euthermic, n= 6) and with (acclimated, n= 7) prior exposure to lower ambient temperatures and shorter photoperiod, simulating adaptation to winter conditions. In both groups of rats, acute hypothermia to T(b)= 25 degrees C shifted the baroreflex-RSNA curve slightly leftwards and downwards with decreases in the setpoint pressure and maximal gain, whereas it markedly impaired the baroreflex-HR curve characterized by decreases in response range by approximately 90% (P < 0.001), minimum response by approximately 10% (P < 0.05) and maximum gain by approximately 95% (P < 0.001), from that at T(b)= 37 degrees C. All parameters were restored to precooling levels on rewarming. Electrical stimulation of cardiac vagal efferents induced a voltage-related bradycardia, the magnitude of which was partially reduced during acute hypothermia, and there was a significant prolongation of the electrocardiogram intervals indicating a delay in cardiac conduction. Mild suppression of baroreflex control of RSNA could contribute to hypothermic hypotension and may primarily reflect an effect of T(b) on central drive. The marked attenuation of the baroreflex control of HR during hypothermia was likely to be due to an impairment of both the central and peripheral components of the reflex arc. Baroreflex control of RSNA and HR was similar between both groups of rats, which implied that the control was non-adaptive on chronic cold exposure.

Acclimatization↗
PubMed2004

Paraventricular nucleus activation of renal sympathetic neurones is synaptically depressed by nitric oxide and glycine acting at a spinal level.

A high density of nitric oxide synthesising enzyme is present in sympathetic preganglionic neurones in the spinal cord. It has been shown that nitric oxide is released as a consequence of synaptic activity. In the present study in anaesthetised rats we determined if nitric oxide acted as a retrograde messenger molecule to modulate the excitatory effects on the renal sympathetic spinal network elicited by paraventricular nucleus stimulation. Neurones in the latter nucleus were stimulated by microinjecting DLH and drugs were applied to the spinal cord via an intrathecal catheter with the tip positioned at T9-T10. Intrathecal application of the nitric oxide donors, sodium nitroprusside or [3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine] significantly increased tonic activity in the renal sympathetic nerve. In contrast synaptic activity evoked by intrathecal glutamate or by paraventricular nucleus stimulation was enhanced by preventing nitric oxide generation with intrathecal N(G)-monomethyl-L-arginine monoacetate (L-NMMA) a nitric oxide synthase inhibitor. Enhancement of synaptically induced renal nerve activity was also observed following intrathecal glycine receptor inhibitor strychnine. Strychnine was without effect when it was given after L-NMMA. It was concluded that paraventricular nucleus excitation of renal sympathetic neurones is subject to inhibitory modulation by released nitric oxide and it is suggested the latter acts via glycine interneurones.

Action Potentials↗
PubMed2003

The influence of vasopressin on tonic activity of cardiovascular neurones in the ventrolateral medulla of the hypertensive rat.

In normotensive Wistar rats, vasopressin may act as an excitatory neurotransmitter at synapses of paraventricular neurones on rostral ventrolateral medullary vasomotor neurones. We studied the influence of this neurotransmitter in spontaneously hypertensive rats to determine if it contributed to the increases in sympathetic nerve traffic in these rats.A five-barrel micropipette assembly was used for extracellular recording of neuronal activity and for microiontophoresis of drugs into the vicinity of identified medullary vasomotor neurones. Excitatory effects of iontophoretically applied vasopressin were blocked by simultaneous iontophoretic application of V(1a) antagonist. Similar application of the vasopressin receptor antagonist did not block an excitatory effect of iontophoretically applied glutamate. Excitatory effects produced by activating paraventricular neurones were also blocked by the V(1a) antagonist. However, the vasopressin antagonist did not alter the ongoing activity of medullary vasomotor neurones. Therefore, in these anaesthetised hypertensive rats, we concluded that vasopressin neurones do not exert a significant tonic drive to rostral ventrolateral medullary-spinal vasomotor neurones.

Animals↗
PubMed2003

Guinea-pig heart acetylcholinesterase after continuous physostigmine administration.

G1 and G4 acetylcholinesterase (AChE) molecular forms were separated in different regions of guinea-pig heart. The activities of both were highest in the left side of the left ventricle (LV(L)). The reversible anticholinesterase physostigmine, or saline, was administered continuously for six days. In saline-treated animals the activity of both molecular forms was markedly increased in both atria, G1 activity was increased on the left side of the right ventricle (LV(R)), and G4 activity was increased on both sides of the right ventricle compared to untreated animals. However, G1 activity was significantly decreased on the left side of the left ventricle. Physostigmine administration caused a significant reduction in G4 activity in the left atrium (LA), the left side of the right ventricle, and the left side of the left ventricle, and a significant increase in G1 activity on the right side of the right ventricle compared to saline-treated animals. The distribution of AChE indicates a role for parasympathetic nerves in the control of both ventricles and atria. The changes in AChE in saline-treated animals could have been due to the anaesthesia or stress of the surgical procedures. Physostigmine caused delayed changes in the enzyme in some regions, consistent with an effect on its expression.

Acetylcholinesterase↗
PubMed2002

Chronotropic effects of nitric oxide in the denervated human heart.

Nitric oxide synthase is expressed in the sino-atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (3 mg kg(-1)) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection of L-NMMA increased mean arterial pressure by 17 +/- 2 mmHg (mean +/- S.E.M.; P < 0.001) and also had a significant negative chronotropic effect, lengthening the R-R interval by 54 +/- 8 ms (P < 0.001). This bradycardia was not reflex in origin since injection of the non-NO-dependent vasoconstrictor, phenylephrine (100 microg) achieved a similar rise in mean arterial pressure (18 +/- 3 mmHg; P < 0.001) but failed to change R-R interval duration (Delta R-R = -3 +/- 4 ms). Furthermore, no change in levels of circulating adrenaline was observed with L-NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose-dependent shortening of R-R interval duration, peak Delta R-R = -25 +/- 8 ms with 130 microg (P < 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino-atrial node.

Cross-Over Studies↗
PubMed2002

Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: a role for mechanoreceptors.

Previous evidence suggests that the heart rate (HR) increase observed with isometric exercise is dependent on different afferent mechanisms to those eliciting the increase in blood pressure (BP). Central command and muscle metaboreceptors have been shown to contribute to this differential effect. However, in experimental animals passive stretch of the hindlimb increases HR suggesting that small fibre mechanoreceptors could also have a role. This has not been previously shown in humans and was investigated in this study. Healthy human volunteers were instrumented to record BP, ECG, respiration, EMG of rectus femoris and gastrocnemius and contraction force of triceps surae. Voluntary isometric contraction of triceps surae elicited a significant HR change in the first three respiratory cycles at 40 % of maximum voluntary contraction whereas BP did not change significantly until after 30 s. This suggests that different mechanisms are involved in the initiation of the cardiovascular changes. Sustained passive stretch of triceps surae for 1 min, by dorsiflexion of the foot, caused a significant (P < 0.05) increase in HR (5 +/- 2.6 beats min(-1)) with no significant change in BP. A time domain measure of cardiac vagal activity was reduced significantly during passive stretch from 69.7 +/- 12.9 to 49.6 +/- 8.9 ms. Rapid rhythmic passive stretch (0.5 Hz for 1 min) was without significant effect suggesting that large muscle proprioreceptors are not involved. We conclude that in man small fibre muscle mechanoreceptors responding to stretch, inhibit cardiac vagal activity and thus increase HR. These afferents could contribute to the initial cardiac acceleration in response to muscle contraction.

Adult↗
PubMed2002

Right atrial stretch induces renal nerve inhibition and c-fos expression in parvocellular neurones of the paraventricular nucleus in rats.

The paraventricular nucleus of the hypothalamus plays a pivotal role in the regulation of plasma volume. Part of the response to an increase in volume load is an inhibition of renal sympathetic nerve activity. The present experiments were designed to determine which subnuclei of the paraventricular nucleus are involved in this sympatho-inhibitory response. Experiments were performed on anaesthetised rats. Activated neurones were recognised by the expression of the early gene c-fos, identified by immunohistochemical labelling of its protein product Fos. Plasma volume loading with 4 % Ficoll 70, using an infusion-withdrawal procedure (2 ml over 1 min) repeated 15 times over 1 h revealed a total of 775 +/- 101 (n = 6) Fos-positive neurones scattered throughout both the magnocellular and parvocellular subnuclei. In comparison, sustained hypertension resulted in 452 +/- 56 (n = 3) Fos-positive neurones similarly distributed, whereas a normotensive control group (n = 3) displayed 115 +/- 18 Fos-positive neurones. Because of this lack of a specific effect we used a more selective stimulation of right atrial receptors via a balloon placed at the junction of the superior vena cava and the right atrium so it did not impede venous return. Inflation of the balloon inhibited renal sympathetic nerve activity (36 +/- 5 %, n = 7) and repetitive inflation over 1 h resulted in c-fos activation of a small number of neurones (54 +/- 14) located only in the parvocellular subnuclei. Whether these are inhibitory interneurones acting within the paraventricular nucleus, or spinally projecting neurones which inhibit or excite renal sympathetic activity by an action in the spinal cord remains to be determined.

Animals↗
PubMed2001

The role of glutamate and vasopressin in the excitation of RVL neurones by paraventricular neurones.

Neurones in the paraventricular nucleus of the hypothalamus project to rostral ventrolateral medullary spinally projecting vasomotor neurones. We studied the excitatory action and the role of glutamate and vasopressin in this pathway in anaesthetised rats. A five barrel micropipette assembly was used for extracellular recording of neuronal activity and for microiontophoresis of drugs into the vicinity of identified medullary vasomotor neurones. Iontophoresis of L-glutamate or vasopressin into the vicinity of a vasomotor neurone increased activity, effects which were blocked by simultaneous iontophoretic application of a glutamate receptor antagonist, or a vasopressin V(1a) antagonist respectively. Paraventricular neurones were activated either by microinjecting D,L-homocysteic acid or by disinhibition by microinjecting bicuculline. The excitatory effects on vasomotor neurones, of paraventricular nucleus stimulation at some sites were prevented by simultaneous microiontophoretic application of kynurenic acid or at other sites by application of V(1a) antagonist. Neither antagonist altered the ongoing activity of the vasomotor neurones. Therefore, glutamate or vasopressin may act as excitatory neurotransmitters at synapses of paraventricular neurones on rostral ventrolateral medullary vasomotor neurones.

Action Potentials↗
PubMed2001

Vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart.

1. Studies of the effect of vagus nerve stimulation on ventricular myocardial function in mammals are limited, particularly in the human. 2. The present study was designed to determine the effect of direct electrical stimulation of the left vagus nerve on left ventricular contractile state in hearts paced at 10 % above the natural rate, in anaesthetised pigs and anaesthetised human subjects undergoing open chest surgery for coronary artery bypass grafting. 3. Contractility of the left ventricle was determined from a series of pressure-volume loops obtained from a combined pressure and conductance (volume) catheter placed in the left ventricle. From the measurements a regression slope of the end-systolic pressure-volume relationship was determined to give end-systolic elastance (Ees), a load-independent measure of contractility. 4. In six anaesthetised open chest pigs, stimulation of the peripheral cut end of the left cervical vagus nerve induced a significant decrease in Ees of 26 +/- 14 %. 5. In nine patients electrical stimulation of the left thoracic vagus nerve close to its cardiac branch resulted in a significant drop in Ees of 38 +/- 16 %. 6. The effects of vagal stimulation were blocked by the muscarinic antagonist glycopyrronium (5 mg kg(-1)). 7. Administration of the beta-adrenoreceptor antagonist esmolol (1 mg kg(-1)) also attenuated the effect of vagal stimulation, indicating a degree of interaction of vagal and sympathetic influences on contractility. 8. These studies show that in the human and pig heart the left vagus nerve can profoundly decrease the inotropic state of the left ventricular myocardium independent of its bradycardic effect.

Animals↗