Autoradiographic studies on binding sites of 3H-Noradrenaline in the gastric fundus of rat: Role in...

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ABSTRACTS: The Autonomic Nervous System 231 Further Studies on Sympathetic Hyperfunction in Motor Neuron Disease Naotoshi Tamura, Kunio Shimazu, Toshimasa Yamamoto, Seietsu Watanabe, Atsuhiro Onoda, Kaori Itokawa and Katsuhiko Hamaguchi Department of Neurology, Saitama Medical Schoo~ Saitama 350-04, Japan While it is generally accepted that there is no involve- ment of the autonomic nervous system in motor neuron disease, some reports have suggested the possibility of an increased sympathetic function. In this study we have therefore examined systematically the sympathetic function in 13 patients with motor neuron disease and in 10 control subjects. These were the main findings: (i) haemodynamic tests showed that the overshoot of the blood pressure in the Valsalva's maneuver was signifi- cantly greater in patients than in controls. The reflex hypertension in response to the cold pressor tests also tended to be elevated among the patients; (ii) the increase in blood pressure following an intravenous administration of noradrenaline was blunted in motor neuron disease patients; (iii) the effects of administra- tion of isoproterenol on pulse rate and blood pressure were not different in patients and in controls; (iv) the plasma noradrenaline level was significantly higher in patients than in controls, whereas the plasma adrenaline level did not differ between the two groups; and (v) patients with motor neuron disease had an increased urinary secretion rate ofvanillylmandelie acid, methoxy- hydroxy-phenylglyeol and normetanephrine, but not of homovanillie acid or metanephrine. These results dearly indicate that in patients with motor neuron disease there is an increased release of noradrenaline from sympathetic nerve fibres. (The Autonomic Nervous System, 28: 357-363, 1991) Chemical Stimulation of the Locus Coeruleus: Inhibi- tory Effects on Blood Pressure, Heart Rate and Renal Sympathetic Nerve Activity Takashi Miyawaki, I-Iiroshi Kawamura and Michinobu Hatano Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173, Japan We studied the role of the locus coeruleus in the regula- tion of arterial pressure, heart rate and renal sympath- etic nerve activity, by means of a microinjection tech- nique in anesthetized rats. Unilateral mieroinjection of the excitatory amino acid L-glutamate into the locus coeruleus increased the neuronal activity of the locus coeruleus and elicited a dose-dependent decrease in blood pressure and heart rate. In response to this chemical stimulation there was also a transient but strong inhibition of the renal sympathetic nerve activity. The responses were not affected by severing the ascend- ing projections of the locus coeruleus with a midbrain o transection. In contrast, injection of the inhibitory amino acid 7-aminobutyric acid (GABA) or the a2-adrenergie agonist clonidine into the locus coeruleus decreased the neuronal activity in this nucleus, but there was no effect on arterial pressure or heart rate. We concluded that: (i) the neurons of the locus eoeruleus exert an inhibitory effect on the sympathetic nervous system, and the chemical stimulation of these neurons elicits a depressor and bradycardic response; (ii) these inhibitory responses are not mediated by the ascending projections of the locus eoeruleus, but by its descending projections; and (iii) the neurons of the locus coeruleus have no tonic effect on the cardiovascular system. (The Autonomic Nervous System, 28: 364-370, 1991) Autoradiographic Studies on Binding Sites of 3H- Not'adrenaline in the Gastric Fundus of Rat: Role in Secretion and Microclrculation Masahiko Nakamura*, Masaya Oda**, Jun Inoue**, Atsuko Morishita**, Takashi Ito**, Yasuo Fujishiro*** and Masaharu Tsuchiya** *Department of Internal Medicine, ***Department of Surgery, Tokyo Demyoku Hospital, Tokyo 160, and **Department of Internal Medicine~ School of Medicine; Keio University, Tokyo 160, Japan We investigated by autoradiography the binding site for 3H-noradmnaline in freeze-dried specimens of rat stomach (autoradiography of the soluble compounds) and in routinely-fLxed specimens, with the aim of clarify- ing the effect ofnoradrenaline on the fundic portion of the stomach. An aqueous solution of 3H-noradrenaline mixed with various concentrations of cold ligand were infused through an intra-aortic catheter. Immediately after the infusion, the stomach was removed and its wall cut into small blocks with a razor blade. For autoradio- graphy of the soluble compounds, the blocks were

Transcript of Autoradiographic studies on binding sites of 3H-Noradrenaline in the gastric fundus of rat: Role in...

ABSTRACTS: The Autonomic Nervous System 231

Further Studies on Sympathetic Hyperfunction in Motor Neuron Disease Naotoshi Tamura, Kunio Shimazu, Toshimasa Yamamoto, Seietsu Watanabe, Atsuhiro Onoda, Kaori Itokawa and Katsuhiko Hamaguchi Department of Neurology, Saitama Medical Schoo~ Saitama 350-04, Japan

While it is generally accepted that there is no involve- ment of the autonomic nervous system in motor neuron disease, some reports have suggested the possibility of an increased sympathetic function. In this study we have therefore examined systematically the sympathetic function in 13 patients with motor neuron disease and in 10 control subjects. These were the main findings: (i) haemodynamic tests showed that the overshoot of the blood pressure in the Valsalva's maneuver was signifi- cantly greater in patients than in controls. The reflex hypertension in response to the cold pressor tests also tended to be elevated among the patients; (ii) the increase in blood pressure following an intravenous administration of noradrenaline was blunted in motor neuron disease patients; (iii) the effects of administra- tion of isoproterenol on pulse rate and blood pressure were not different in patients and in controls; (iv) the plasma noradrenaline level was significantly higher in patients than in controls, whereas the plasma adrenaline level did not differ between the two groups; and (v) patients with motor neuron disease had an increased urinary secretion rate ofvanillylmandelie acid, methoxy- hydroxy-phenylglyeol and normetanephrine, but not of homovanillie acid or metanephrine. These results dearly indicate that in patients with motor neuron disease there is an increased release of noradrenaline from sympathetic nerve fibres.

(The Autonomic Nervous System, 28: 357-363, 1991)

Chemical Stimulation of the Locus Coeruleus: Inhibi- tory Effects on Blood Pressure, Heart Rate and Renal Sympathetic Nerve Activity Takashi Miyawaki, I-Iiroshi Kawamura and Michinobu Hatano Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173, Japan

We studied the role of the locus coeruleus in the regula- tion of arterial pressure, heart rate and renal sympath-

etic nerve activity, by means of a microinjection tech- nique in anesthetized rats. Unilateral mieroinjection of the excitatory amino acid L-glutamate into the locus coeruleus increased the neuronal activity of the locus coeruleus and elicited a dose-dependent decrease in blood pressure and heart rate. In response to this chemical stimulation there was also a transient but strong inhibition of the renal sympathetic nerve activity. The responses were not affected by severing the ascend- ing projections of the locus coeruleus with a midbrain

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transection. In contrast, injection of the inhibitory amino acid 7-aminobutyric acid (GABA) or the a2-adrenergie agonist clonidine into the locus coeruleus decreased the neuronal activity in this nucleus, but there was no effect on arterial pressure or heart rate. We concluded that: (i) the neurons of the locus eoeruleus exert an inhibitory effect on the sympathetic nervous system, and the chemical stimulation of these neurons elicits a depressor and bradycardic response; (ii) these inhibitory responses are not mediated by the ascending projections of the locus eoeruleus, but by its descending projections; and (iii) the neurons of the locus coeruleus have no tonic effect on the cardiovascular system.

(The Autonomic Nervous System, 28: 364-370, 1991)

Autoradiographic Studies on Binding Sites of 3H- Not'adrenaline in the Gastric Fundus of Rat: Role in Secretion and Microclrculation Masahiko Nakamura*, Masaya Oda**, Jun Inoue**, Atsuko Morishita**, Takashi Ito**, Yasuo Fujishiro*** and Masaharu Tsuchiya** *Department of Internal Medicine, ***Department of Surgery, Tokyo Demyoku Hospital, Tokyo 160, and **Department of Internal Medicine~ School of Medicine; Keio University, Tokyo 160, Japan

We investigated by autoradiography the binding site for 3H-noradmnaline in freeze-dried specimens of rat stomach (autoradiography of the soluble compounds) and in routinely-fLxed specimens, with the aim of clarify- ing the effect ofnoradrenaline on the fundic portion of the stomach. An aqueous solution o f 3H-noradrenaline mixed with various concentrations of cold ligand were infused through an intra-aortic catheter. Immediately after the infusion, the stomach was removed and its wall cut into small blocks with a razor blade. For autoradio- graphy of the soluble compounds, the blocks were

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quickly frozen in isopentane cooled to its melting point in liquid nitrogen. The autoradiographic procedure was carried out by direct embedding in Epon, by wet-sec- tioning with ethylene glycol, and by dry-mounting the emulsion film with a wire loop to prevent loss of the labeled substance. Specific binding sites for SH- noradrenaline were found on the parietal, chief and enterochromaffin-like cells in the fundic glands, indicat- ing a direct effect of noradrenaline on gastric secretion. Noradrenaline-binding sites were also found on smooth muscle cells and on the endothelial cells of arterioles and venules in the basal portion of the gastric mucosa and in the submucosa; it is therefore possible that endothelial cells play some role in the vasoconstriction induced by noradrenaline. The number of binding sites on the parietal cells was markedly higher in freeze-dried specimens than in routinely-fixed specimens. Our results indicate that sympathetic nerves may have a direct regulatory effect on secretion and microcirculation in the gastric mucosa.

(The Autonomic Nervous System, 28." 371-382, 1991)

A Case of Acute Idiopathic Pandysautonomia with Severe Visual Disturbance Yuko Sugishita, Marl Mugishima, Itsuro Kobayashi, Toshiko Tekemiya and Shoich Maruyama Department of Neurology, Neurological Institute, Tokyo Women's Medical College, Tokyo 162, Japan

We present the case of a 30-year-old woman who was admitted to our hospital because of a syncopal attack on standing, and abdominal bulging. After presenting symptoms similar to those of a common cold, the patient experienced severe back pain, nausea, and had hypohydrosis followed by severe orthostatic hypotension, ileus and salivary and lacrimal hyposecretion for about two weeks. Ten days after onset of the syndrome, the visual acuity in the right eye was severely compromised and that in the left eye was reduced. On admission, cerebrospinal fluid analysis showed albumino-cytological dissociation, and the Ebstein-Barr virus titer in serum and cerebrospinal fluid was raised. Functional tests of the autonomic nervous system revealed that the main lesion was situated in the post-ganglionic nerves. We diagnosed this case as acute idiopathic pandysauto- nomia, in spite of the fact that there had been no previous reports of severe visual disturbance in this disease. We suppose that in this case the visual dis- turbance was to isehemic changes in the optic nerves. The patient had been diagnosed to have dermato- myositis two years ago, and we suspected that the acute

idiopathic pandysautonomia and the dermatomyositis had a common autoimmunological origin.

(The Autonomic Nervous System, 28: 383-387, 1991)

Effects of Autonomic Blocking Agents and Vagotomy on the Circulatory Response to the Valsalva Maneuver in Rabbits Katsumasa Goto, Kunihiro Sannomiya and Toru Okajima Third Department of Medicine, Medical College of Oita, Oita 879-55, Japan

We investigated the effects of the t~-adrenergic antagon- ist phentolamine, the B-adrenergic antagonist propra- nolol, the parasympathetic antagonist atropine, and vagotomy on the circulatory response to the Valsalva maneuver. Arterial blood pressure and pulse rate were continuously monitored in 24 rabbits under light anes- thesia with secobarbital sodium. The Valsalva maneuver was performed by applying, for 10 seconds during expi- ration, a pressure of 10 mm Hg to the tracheal cannula linked with a sphygmomanometer cuff around thorax and abdomen. The following results were obtained: (i) after injection of phentolamine, the baseline systolic pressure decreased and the pulse rate increased. The tachycardia of phase II of the Valsalva maneuver was significantly reduced, and so were the overshoot and the reflex bradycardia of phase IV; (ii) after propranolol, the systolic pressure was unchanged, whereas the pulse rate decreased. The tachycardia of phase II and the overshoot and reflex bradycardia of phase IV decreased significantly; (iii) after a small dose of atropine, systolic pressure and pulse rate were unchanged. The tachycardia of phase II was significantly reduced, whereas overshoot and reflex bradycardia of phase IV were unaffected. After a large dose of atropine, there was a slight decrease in blood pressure; the increase in pulse rate was not significant. There was also a signifi- cant reduction of phase II tachycardia and of phase IV bradycardia, and a slight reduction of phase IV over- shoot; and (iv) after vagotomy, pulse rate was increased and blood pressure was unchanged. There was a signifi- cant reduction of phase II tachyeardia and phase IV overshoot and bradycardia. We concluded that a- adrenergic,13-adrenergic and parasympathetic systems all participate in the circulatory response to the Valsalva maneuver.

(The Autonomic Nervous System, 28: 388-398, 1991)