Kanji Matsukawa

The amplitude of synchronized cardiac sympathetic nerve activity reflects the number of activated pre- and postganglionic fibers in anesthetized cats

In order to obtain information regarding the number of pre- and postganglionic fibers that are firing, we measured cardiac sympathetic nerve activity (CSNA) before and after the successive sectioning of T1-T5 thoracic rami in anesthetized cats. Total activity from the area was measured under the mean CSNA curve. Peak amplitude, width and periodicity of the synchronized discharge was analyzed from the CSNA curve by the method we developed. Total CSNA decreased to 91 +/- 6%, 63 +/- 6%, 27 +/- 10%, 8 +/- 6% and < 1% of the control due to successive section of the T5, T4, T3, T2 and T1 rami, respectively. The peak amplitude of synchronized CSNA decreased to 95 +/- 6%, 73 +/- 8%, 40 +/- 5% and < 10% of the control value, due to section of the T5, T4, T3 and T2 rami, respectively. The control width was 107 +/- 8 ms and decreased to 106 +/- 1 ms, 92 +/- 6 ms and 68 +/- 5 ms by successive section of the respective T5, T4 and T3 rami. However, periodicities of 80-120 ms (Tc rhythm) and 140-500 ms (Tb rhythm) of synchronized CSNA remained unchanged after section of the T3-T5 rami. The total CSNA decreased gradually due to decreases in the peak amplitude and width of synchronized CSNA with the successive section of preganglionic fibers. These results indicate that the peak amplitude of synchronized CSNA reflects the number of pre- and post-ganglionic fibers that are firing and suggest that the number of preganglionic neurons which activate the cardiac fibers naturally was largest in the T3 segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular–premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command‐evoked inhibition of the aortic baroreceptor–heart rate reflex blunted the baroreflex‐mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long‐lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Augmented renal sympathetic nerve activity by central command during overground locomotion in decerebrate cats

We examined whether the cerebrum is essential for producing the rapid autonomic adjustment at the onset of spontaneous overground locomotion. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and electromyogram of the forelimb triceps brachialis were measured when freely moving, decerebrate cats spontaneously produced overground locomotion, supporting body weight. Decerebration was performed at the level of the precollicular-premammillary body. RSNA increased 95 ± 14 impulses/s (68 ± 10% of baseline value) at the onset of spontaneous locomotion, which was followed by rises in MAP and HR (7 ± 1 mmHg and 18 ± 2 beats/min, respectively). Concomitantly with the MAP rise, RSNA declined toward control values and then increased again during the subsequent period of locomotion. The same rapid increase in RSNA at the onset of locomotion was observed after sinoaortic denervation and vagotomy. It is concluded that some central site(s), other than the cerebrum and the rostral part of the diencephalon, can generate the centrally induced autonomic adjustment at the onset of spontaneous overground locomotion, which is independent of arterial baroreceptor and vagal afferents.We examined whether the cerebrum is essential for producing the rapid autonomic adjustment at the onset of spontaneous overground locomotion. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and electromyogram of the forelimb triceps brachialis were measured when freely moving, decerebrate cats spontaneously produced overground locomotion, supporting body weight. Decerebration was performed at the level of the precollicular-premammillary body. RSNA increased 95 +/- 14 impulses/s (68 +/- 10% of baseline value) at the onset of spontaneous locomotion, which was followed by rises in MAP and HR (7 +/- 1 mmHg and 18 +/- 2 beats/min, respectively). Concomitantly with the MAP rise, RSNA declined toward control values and then increased again during the subsequent period of locomotion. The same rapid increase in RSNA at the onset of locomotion was observed after sinoaortic denervation and vagotomy. It is concluded that some central site(s), other than the cerebrum and the rostral part of the diencephalon, can generate the centrally induced autonomic adjustment at the onset of spontaneous overground locomotion, which is independent of arterial baroreceptor and vagal afferents.

Direct observations of sympathetic cholinergic vasodilatation of skeletal muscle small arteries in the cat.

1. The aim of this study was to examine the actual changes of the internal diameter (i.d.) of arterial vessels of skeletal muscle evoked by activation of sympathetic cholinergic nerve fibres during stimulation of the hypothalamic defence area in anaesthetized cats. 2. For this purpose, we have used our novel X‐ray TV system for visualizing small arteries (100‐500 microm i.d.) of the triceps surae muscle and larger extramuscular arteries (500‐1400 microm i.d.) of the hindlimb (the femoral (FA), popliteal (PA) and distal caudal femoral (DCFA) arteries). The passage of a contrast medium from the large extramuscular arteries to the smaller intramuscular arteries was serially measured before and during hypothalamic stimulation. 3. Hypothalamic stimulation increased mean arterial blood pressure, heart rate and femoral vascular conductance. The i.d. of FA, PA, and DCFA did not change during the hypothalamic stimulation, whereas the i.d. of small arteries in the triceps surae muscle increased by 48 +/‐ 2% (mean +/‐ S.E.M.) and the cross‐sectional area increased concomitantly by 118%. The maximum increase in i.d. of 78 +/‐ 6%, was observed in arteries of 100‐200 microm. These increases in diameter were markedly reduced by intra‐arterial injection of atropine or by cutting the sciatic nerve, but not by phentolamine and propranolol given together. 4. The vasodilatation evoked by hypothalamic stimulation was seen in almost all the sections of the small arteries observed under control conditions and was distributed along the entire length of the vessel. In addition, the number of arterial vessels that could be detected increased by 42% during hypothalamic stimulation. The newly detected arterial branches, which ranged from 100 to 300 microm in diameter, mostly arose from the branching points. 5. It is concluded that stimulation of sympathetic cholinergic nerve fibres dilates the small arteries of skeletal muscle ranging from 100 to 500 microm, but not the larger extramuscular arteries.

Effects of mental stress on cardiac and motor rhythms

To identify whether spontaneous cardiac rhythm and voluntary motor rhythm are modified in parallel or influenced separately when imposing mental stress, we recorded simultaneously the two rhythms during finger tapping as a simple model of rhythmical motion in 10 healthy human subjects (6 males, 4 females each). Each subject performed finger tapping with an arbitrary tapping rhythm. Mental stress was given intermittently three times for 10-15 s at intervals of 40 s during tapping for 150 s. Heart rate (HR) and tapping rate (TR) and their variations (standard deviation; SD) during finger tapping with and without mental stress were compared. HR and TR increased significantly in response to mental stress during tapping. After mental stress was ended, HR returned rapidly to the initial level, but TR remained at a higher level. Moreover, SD of TR, but not SD of HR, during tapping was increased by mental stress. The present results indicate that the cardiac and motor rhythms are influenced simultaneously by mental stress. However, a difference was seen about the sustained effect of mental stress on the two rhythms.

Coactivation of renal sympathetic neurons and somatic motor neurons by chemical stimulation of the midbrain ventral tegmental area

We examined whether neurons in the midbrain ventral tegmental area (VTA) play a role in generating central command responsible for autonomic control of the cardiovascular system in anesthetized rats and unanesthetized, decerebrated rats with muscle paralysis. Small volumes (60 nl) of an N-methyl-D-aspartate receptor agonist (L-homocysteic acid) and a GABAergic receptor antagonist (bicuculline) were injected into the VTA and substantia nigra (SN). In anesthetized rats, L-homocysteic acid into the VTA induced short-lasting increases in renal sympathetic nerve activity (RSNA; 66 ± 21%), mean arterial pressure (MAP; 5 ± 2 mmHg), and heart rate (HR; 7 ± 2 beats/min), whereas bicuculline into the VTA produced long-lasting increases in RSNA (130 ± 45%), MAP (26 ± 2 mmHg), and HR (66 ± 6 beats/min). Bicuculline into the VTA increased blood flow and vascular conductance of the hindlimb triceps surae muscle, suggesting skeletal muscle vasodilatation. However, neither drug injected into the SN affected all variables. Renal sympathetic nerve and cardiovascular responses to chemical stimulation of the VTA were not essentially affected by decerebration at the premammillary-precollicular level, indicating that the ascending projection to the forebrain from the VTA was not responsible for evoking the sympathetic and cardiovascular responses. Furthermore, bicuculline into the VTA in decerebrate rats produced long-lasting rhythmic bursts of RSNA and tibial motor nerve discharge, which occurred in good synchrony. It is likely that the activation of neurons in the VTA is capable of eliciting synchronized stimulation of the renal sympathetic and tibial motor nerves without any muscular feedback signal.

Central command does not decrease cardiac parasympathetic efferent nerve activity during spontaneous fictive motor activity in decerebrate cats

To examine whether withdrawal of cardiac vagal efferent nerve activity (CVNA) predominantly controls the tachycardia at the start of exercise, the responses of CVNA and cardiac sympathetic efferent nerve activity (CSNA) were directly assessed during fictive motor activity that occurred spontaneously in unanesthetized, decerebrate cats. CSNA abruptly increased by 71 ± 12% at the onset of the motor activity, preceding the tachycardia response. The increase in CSNA lasted for 4-5 s and returned to the baseline, even though the motor activity was not ended. The increase of 6 ± 1 beats/min in heart rate appeared with the same time course of the increase in CSNA. In contrast, CVNA never decreased but increased throughout the motor activity, in parallel with a rise in mean arterial blood pressure (MAP). The peak increase in CVNA was 37 ± 9% at 5 s after the motor onset. The rise in MAP gradually developed to 21 ± 2 mmHg and was sustained throughout the spontaneous motor activity. Partial sinoaortic denervation (SAD) blunted the baroreflex sensitivity of the MAP-CSNA and MAP-CVNA relationship to 22-33% of the control. Although partial SAD blunted the initial increase in CSNA to 53% of the control, the increase in CSNA was sustained throughout the motor activity. In contrast, partial SAD almost abolished the increase in CVNA during the motor activity, despite the augmented elevation of 31 ± 1 mmHg in MAP. Because afferent inputs from both muscle receptors and arterial baroreceptors were absent or greatly attenuated in the partial SAD condition, only central command was operating during spontaneous fictive motor activity in decerebrate cats. Therefore, it is likely that central command causes activation of cardiac sympathetic outflow but does not produce withdrawal of cardiac parasympathetic outflow during spontaneous motor activity.

Central command contributes to increased blood flow in the noncontracting muscle at the start of one-legged dynamic exercise in humans

Whether neurogenic vasodilatation contributes to exercise hyperemia is still controversial. Blood flow to noncontracting muscle, however, is chiefly regulated by a neural mechanism. Although vasodilatation in the nonexercising limb was shown at the onset of exercise, it was unclear whether central command or muscle mechanoreflex is responsible for the vasodilatation. To clarify this, using voluntary one-legged cycling with the right leg in humans, we measured the relative changes in concentrations of oxygenated-hemoglobin (Oxy-Hb) of the noncontracting vastus lateralis (VL) muscle with near-infrared spectroscopy as an index of tissue blood flow and femoral blood flow to the nonexercising leg. Oxy-Hb in the noncontracting VL and femoral blood flow increased (P < 0.05) at the start period of voluntary one-legged cycling without accompanying a rise in arterial blood pressure. In contrast, no increases in Oxy-Hb and femoral blood flow were detected at the start period of passive one-legged cycling, suggesting that muscle mechanoreflex cannot explain the initial vasodilatation of the noncontracting muscle during voluntary one-legged cycling. Motor imagery of the voluntary one-legged cycling increased Oxy-Hb of not only the right but also the left VL. Furthermore, an increase in Oxy-Hb of the contracting VL, which was observed at the start period of voluntary one-legged cycling, had the same time course and magnitude as the increase in Oxy-Hb of the noncontracting muscle. Thus it is concluded that the centrally induced vasodilator signal is equally transmitted to the bilateral VL muscles, not only during imagery of exercise but also at the start period of voluntary exercise in humans.

Centrally evoked increase in adrenal sympathetic outflow elicits immediate secretion of adrenaline in anaesthetized rats.

To examine whether feedforward control by central command activates preganglionic adrenal sympathetic nerve activity (AdSNA) and releases catecholamines from the adrenal medulla, we investigated the effects of electrical stimulation of the hypothalamic locomotor region on preganglionic AdSNA and secretion rate of adrenal catecholamines in anaesthetized rats. Pre‐ or postganglionic AdSNA was verified by temporary sympathetic ganglionic blockade with trimethaphan. Adrenal venous blood was collected every 30 s to determine adrenal catecholamine output and blood flow. Hypothalamic stimulation for 30 s (50 Hz, 100–200 μA) induced rapid activation of preganglionic AdSNA by 83–181% depending on current intensity, which was followed by an immediate increase of 123–233% in adrenal adrenaline output. Hypothalamic stimulation also increased postganglionic AdSNA by 42–113% and renal sympathetic nerve activity by 94–171%. Hypothalamic stimulation induced preferential secretion of adrenal adrenaline compared with noradrenaline, because the ratio of adrenaline to noradrenaline increased greatly during hypothalamic stimulation. As soon as the hypothalamic stimulation was terminated, preganglionic AdSNA returned to the prestimulation level in a few seconds, and the elevated catecholamine output decayed within 30–60 s. Adrenal blood flow and vascular resistance were not affected or slightly decreased by hypothalamic stimulation. Thus, it is likely that feedforward control of catecholamine secretion from the adrenal medulla plays a role in conducting rapid hormonal control of the cardiovascular system at the beginning of exercise.

Origin of cardiac-related synchronized cardiac sympathetic nerve activity in anaesthetized cats

To study the origin of cardiac-related rhythm in cardiac sympathetic nerve activity (CSNA), ECG, aortic pressure and CSNA were recorded when cardiac interval was changed by artificial pacing, or when the aortic nerve was stimulated after baroreceptor denervation in anaesthetized cats. CSNA was averaged by using the R-wave of ECG, or stimulus pulse as a trigger. Delay times from arterial pulse or stimulus pulse to the onset and half amplitude of inhibition and to the maximal inhibition were measured from the averaged data. The delay of inhibition in CSNA was constant and independent of pacing interval. Stimulation of the aortic nerve with single shocks caused an inhibition in averaged CSNA. The delay of inhibition was constant and independent of stimulus frequency. These results indicate that the cardiac-related rhythm in CSNA is produced reflexly by inhibiting the transmission of the fundamental rhythmicity due to periodic baroreceptor input.