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REM sleep behavior disorders in neurodegenerative disease
108 using: (1) a traditional battery of cardiovascular autonomic tests based on heart rate variations during Valsalva Manoeuvre (VR), Lying-to-Standing (LS), Standing-toLying (late phase: SL2), Deep Breathing DB and (2) Power Spectral Analysis (PSA) of heart rate variations lying and standing. The results showed a comparable response in VR, DB in controls and glaucoma patients while LS and especially SL2, in these latter, differed significantly (1.14 (0.10) vs. 1.24 (0.16), P<0.05; 1.22 (0.12) vs. 1.39 (0.16), P < 0.001, respectively). Moreover, PSA at Low Frequency Bands (LF) differed with high significance in glaucoma patients lying and standing (231 (230) vs. 1197 (1192), P<0.001 and 202 (205) vs. 613 (631), P < 0.02) while it differed at High Frequency Bands (HF) only lying (101 (143) vs. 416 (424), P<0.005). On standing L F / H F ratio also differed in glaucoma patients (5.70 (1.1) vs. 3.72 (0.7), P<0.02). As SL2 and LF on PSA are thought to express sympathetic activity we can argue that glaucoma patients are characterized by systemic dysautonomia with a prevalent sympathetic failure which may play an important role in the onset of chronic ocular hypertension. 136
#z-Adreaergic Drugs Mohinte Pkagneyteeis of Splenic Macro~ages in Normete~ve and HylpertemsiveRats M. Serio l, M.A. Potenza l, E. Jirillo 2 and D. MitoloChieppa 1
Institutes of 1Pharmacology, and 2Microbiology, Medical School, University of Bari, 70124 Bari, Italy The existence of B-adrenergic receptors for neurotransmitters on lymphoeytes, monocytes/macrophages and granulocytes was established and in particular, catecholamines were found to be able to modulate responses of immune cells. In this respect, it is well known that stress and elevated levels of circulating catecholamines produce immunosuppression [1] and, moreover, hypertensive rats exhibit reduced phagocytic capacity during the development of hypertension [2]. On these grounds, we have evaluated the effect of agonists and antagonists of fl2-adrenergic receptors on phagocytosis of C. albicans by splenic maerophages in normotensive rats. Splenic macrophages were preincubated for 30 min at 37"C with isoproterenol alone and with isoproterenol and propranolol, and then phagocytosis was evaluated. Results show that: (1) treatment with isoproterenol alone was associated with reduction of phagocytic capacity; and (2) addition of propranolol antagonized the effect of isoproterenol. These findings suggest that modulation of B2-adrenergic receptors by agonists and antagonists may explain changes of phagocytic activity which we have observed in hypertensive rats. ([1] R. Ader, D. Felten
and N. Cohen. Annu. Rev. Pharmacol. Toxicol. 30, 561602, 1990; [2] M. Serio, M.A. Potenza, M.R. CarratfL V. Vulpis, E. Jirillo, A. Pirrelli, D. Mitolo-Chieppa. Pharmacol. Res. Comm. 26 Suppl. 1,246, 1992.) 137
Twenty-four Hour Hemody-ammicand Temperature Profde in Obstructive Sleep Almea Symdrome: the Effect of Sltortterm CPAP Therapy E. Sforza, G. Addati and E. Lugaresi
Sleep Center, Neurological Institute, University of Bologna, 40123 Bologna, Italy Patients with Obstructive Sleep Apnea syndrome (OSAS) have an abnormal circadian pattern of systemic blood pressure (BP). Similarly, temperature rhythm may be affected. To investigate the temperature (T) and heinedynamic nycthemeral rhythm in OSAS we studied 10 patients during a diagnostic night (NCPAP) and during the first night with CPAP therapy (CPAP). Compared with control subjects, OSAS patients showed higher values of Tand hemodynamic parameters during dayt'une and nighttime. During the NCPAP night the T remained stable without the nadir at the onset of sleep ( P < 0.02) and between 3 and 5 a.m. (P<0.005). During CPAP night T decrease at the start of sleep with a nadir at 3 and 5 a.m. correlated with the major concentration of REM sleep. During NCPAP night BP and heart rate (HR) increased from wakefulness to sleep without the physiological fall. During CPAP night BP and HR decreased compared with the diagnostic night with a significant fall between 11 p.m. and 4 a.m. for diastolic pressure (P<0.05) and HR (P<0.005). Our results showed that OSAS patients had a high nocturnal hemodynamic and temperature profile. Reversal of these changes by short-term CPAP therapy suggests that sleep fragmentation and mechanical and chemical effects due to apnea play a major role in the circadian rhythm abnormalities. 138 REM Sleep Bekavlur Dfmmlers in Nemmle~mer~ive
Disease E. Sforzal, P. Cortelli, P. Martinelli and E. Lugaresi l
1Sleep Center, Institute of Neurology, University of Bologna, 40123 Bologna, Italy REM sleep behavior disorders constitute a recent parasomnia described in patients with neurological disease characterized by the absence of muscle atonia during REM sleep and nocturnal motor behavior connectedwith a dream. We examined 51 subjects referred for abnormal motor activity during sleep. 39 subjects had neurological
109 disease whereas 12 patients were idiopathic. All subjects underwent polysomnography. Video monitoring was done by the night technician who entered in the room and made notes during the recording of abnormal motor activity. REM sleep behavior signs were evident in patients with neurodegenerative disease involving the autonomic system and particularly MSA, PAF and Parkinsonism plus autonomic failure. No abnormal motor activity during REM sleep was recorded in patients with supranuclear palsy and dementia. Video analysis showed a wide range of motor activity from simple jerks and screaming to complex motor activity such as jumping, talking, finger pointing, hand waving and getting out of bed. Video offers clear examples of simplex and complex motor events, Our results confirm previous reports on the high incidence of REM sleep behavior disorders in neurodegenerative disease. The predominant incidence in patients with autonomic failure suggests the role of pontomesencephalic lesions in the genesis of the parasomnia.
139 Parasympathetic Innervation Inhibits Sympathetic Neorotransmission but Exerts Only Minor Direct Effects on Periorbital Smooth Muscle Tone P.G. Smith and C. Beauregard
Department of Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA Orbital vascular and nonvascular smooth muscles receive their primary excitatory innervation from the sympathetic nervous system. Although these targets also typically contain parasympathetic innervation, its function remains unclear. In the present study in rats, we investigated the effects of parasympathetic nerve stimulation on periorbital smooth muscle tone. Parasympathetic innervation was stimulated with an electrode placed stereotaxically in the ipsilateral superior salivatory nucleus while tension was recorded from the periorbital superior tarsal smooth muscle. Parasympathetic stimulation (0,75 V, 20 Hz) caused a small decrease in tension (-73 4-9 mg), which was not altered when muscles were partially contracted by the a-adrenoceptor agonist, methoxamine. However, contractions induced by ipsilateral cervical sympathetic nerve stimulation (1-8 Hz, 10 V) were diminished in a frequency-dependent manner (-338 4- 35 mg at 8 Hz). This inhibition was blocked by atropine methyl nitrate (0.4 mg/kg, i.v.). We conclude that the parasympathetically mediated decrease in tarsal muscle tension observed during sympathetic stimulation is due to cholinergic prejunctional inhibition of sympathetic neurotransmission. This study therefore provides evi-
dence that, in some targets, the principal action of parasympathetic innervation is mediated indirectly via an inhibitory effect on heterologous excitatory nerves. (Supported by NIH NS23502.) 140 Relationship Between Autonomic Neuropathy, 24 h Blood Pressure and Nephropathy in Normotensive Insulin-Dependent Diabetic Patients V. Spallone 1, S. Gambardella 1, M.R. Maiellol, A. Barini 2, S. Frontoni z and G. Menzinger l
~Endocrinology, Department of Internal Medicine, Tor Vergata University and 2Catholic University, Rome, Italy To evaluate whether the association between autonomic neuropathy and nephropathy in insulin-dependent diabetes mellitus has pathogenetic implications, we simultaneously measured 24-h blood pressure (BP) and urinary albumin excretion rate (UAE) on timed overnight and 2-h periods during the day urine collections. We studied 25 normotensive type I diabetic patients without overt nephropathy, divided into two groups, matched for age, duration of diabetes and HbAb according to the presence of cardiovascular autonomic neuropathy (AN). Mean day (08-22) and night (22-08) systolic (SBP) and diastolic BP (DBP), and UAE did not significantly differ between the groups. Nocturnal percentage decrease (A day-night) in SBP, DBP and UAE were significantly lower in patients with AN compared to those without (SBP: 4.17 + 5 vs. 9.77+4.2%, P<0.004; DBP: 9.85-t-5.7 vs. 15.52+5.5, P<0.01; UAE: -13.74-112.1 vs. 44.94-30.4, P<0.04). A day-night in SBP, DBP, and UAE were inversely related to autonomic score, index of AN degree (r= -0.39, P<0.05; r=-0.55, P<0.01; and r : - 0 . 4 8 , P<0.015, respectively). 2-h day period, day and night UAE were similar in the two groups but were more strongly related, respectively, to mean 2 h (r:0.72, P<0.0001), day (r=0,78, P<0.02) and night SBP (r---0.86, P<0.02) in subjects with AN than in those without (2 h: r = 0.30, P < 0.002; day: r = 0.37, NS; night: r=0.38, NS). AN is associated with reduced nocturnal decrease in BP and in UAE. The stronger relation of UAE to SBP in diabetic patients with AN might suggest that the loss of neural control enhances kidney vulnerability to hemodynamic effects of BP. 141 Neurogenic Orthostatic Hypertension N. Tamura, K. Shimazu, S. Watanabe, K. Itokawa, A. Maeda and K. Hamaguchi
Department of Neurology, Saitama Medical School, Saitama 350-04, Japan
#z-Adreaergic Drugs Mohinte Pkagneyteeis of Splenic Macro~ages in Normete~ve and HylpertemsiveRats M. Serio l, M.A. Potenza l, E. Jirillo 2 and D. MitoloChieppa 1
Institutes of 1Pharmacology, and 2Microbiology, Medical School, University of Bari, 70124 Bari, Italy The existence of B-adrenergic receptors for neurotransmitters on lymphoeytes, monocytes/macrophages and granulocytes was established and in particular, catecholamines were found to be able to modulate responses of immune cells. In this respect, it is well known that stress and elevated levels of circulating catecholamines produce immunosuppression [1] and, moreover, hypertensive rats exhibit reduced phagocytic capacity during the development of hypertension [2]. On these grounds, we have evaluated the effect of agonists and antagonists of fl2-adrenergic receptors on phagocytosis of C. albicans by splenic maerophages in normotensive rats. Splenic macrophages were preincubated for 30 min at 37"C with isoproterenol alone and with isoproterenol and propranolol, and then phagocytosis was evaluated. Results show that: (1) treatment with isoproterenol alone was associated with reduction of phagocytic capacity; and (2) addition of propranolol antagonized the effect of isoproterenol. These findings suggest that modulation of B2-adrenergic receptors by agonists and antagonists may explain changes of phagocytic activity which we have observed in hypertensive rats. ([1] R. Ader, D. Felten
and N. Cohen. Annu. Rev. Pharmacol. Toxicol. 30, 561602, 1990; [2] M. Serio, M.A. Potenza, M.R. CarratfL V. Vulpis, E. Jirillo, A. Pirrelli, D. Mitolo-Chieppa. Pharmacol. Res. Comm. 26 Suppl. 1,246, 1992.) 137
Twenty-four Hour Hemody-ammicand Temperature Profde in Obstructive Sleep Almea Symdrome: the Effect of Sltortterm CPAP Therapy E. Sforza, G. Addati and E. Lugaresi
Sleep Center, Neurological Institute, University of Bologna, 40123 Bologna, Italy Patients with Obstructive Sleep Apnea syndrome (OSAS) have an abnormal circadian pattern of systemic blood pressure (BP). Similarly, temperature rhythm may be affected. To investigate the temperature (T) and heinedynamic nycthemeral rhythm in OSAS we studied 10 patients during a diagnostic night (NCPAP) and during the first night with CPAP therapy (CPAP). Compared with control subjects, OSAS patients showed higher values of Tand hemodynamic parameters during dayt'une and nighttime. During the NCPAP night the T remained stable without the nadir at the onset of sleep ( P < 0.02) and between 3 and 5 a.m. (P<0.005). During CPAP night T decrease at the start of sleep with a nadir at 3 and 5 a.m. correlated with the major concentration of REM sleep. During NCPAP night BP and heart rate (HR) increased from wakefulness to sleep without the physiological fall. During CPAP night BP and HR decreased compared with the diagnostic night with a significant fall between 11 p.m. and 4 a.m. for diastolic pressure (P<0.05) and HR (P<0.005). Our results showed that OSAS patients had a high nocturnal hemodynamic and temperature profile. Reversal of these changes by short-term CPAP therapy suggests that sleep fragmentation and mechanical and chemical effects due to apnea play a major role in the circadian rhythm abnormalities. 138 REM Sleep Bekavlur Dfmmlers in Nemmle~mer~ive
Disease E. Sforzal, P. Cortelli, P. Martinelli and E. Lugaresi l
1Sleep Center, Institute of Neurology, University of Bologna, 40123 Bologna, Italy REM sleep behavior disorders constitute a recent parasomnia described in patients with neurological disease characterized by the absence of muscle atonia during REM sleep and nocturnal motor behavior connectedwith a dream. We examined 51 subjects referred for abnormal motor activity during sleep. 39 subjects had neurological
109 disease whereas 12 patients were idiopathic. All subjects underwent polysomnography. Video monitoring was done by the night technician who entered in the room and made notes during the recording of abnormal motor activity. REM sleep behavior signs were evident in patients with neurodegenerative disease involving the autonomic system and particularly MSA, PAF and Parkinsonism plus autonomic failure. No abnormal motor activity during REM sleep was recorded in patients with supranuclear palsy and dementia. Video analysis showed a wide range of motor activity from simple jerks and screaming to complex motor activity such as jumping, talking, finger pointing, hand waving and getting out of bed. Video offers clear examples of simplex and complex motor events, Our results confirm previous reports on the high incidence of REM sleep behavior disorders in neurodegenerative disease. The predominant incidence in patients with autonomic failure suggests the role of pontomesencephalic lesions in the genesis of the parasomnia.
139 Parasympathetic Innervation Inhibits Sympathetic Neorotransmission but Exerts Only Minor Direct Effects on Periorbital Smooth Muscle Tone P.G. Smith and C. Beauregard
Department of Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA Orbital vascular and nonvascular smooth muscles receive their primary excitatory innervation from the sympathetic nervous system. Although these targets also typically contain parasympathetic innervation, its function remains unclear. In the present study in rats, we investigated the effects of parasympathetic nerve stimulation on periorbital smooth muscle tone. Parasympathetic innervation was stimulated with an electrode placed stereotaxically in the ipsilateral superior salivatory nucleus while tension was recorded from the periorbital superior tarsal smooth muscle. Parasympathetic stimulation (0,75 V, 20 Hz) caused a small decrease in tension (-73 4-9 mg), which was not altered when muscles were partially contracted by the a-adrenoceptor agonist, methoxamine. However, contractions induced by ipsilateral cervical sympathetic nerve stimulation (1-8 Hz, 10 V) were diminished in a frequency-dependent manner (-338 4- 35 mg at 8 Hz). This inhibition was blocked by atropine methyl nitrate (0.4 mg/kg, i.v.). We conclude that the parasympathetically mediated decrease in tarsal muscle tension observed during sympathetic stimulation is due to cholinergic prejunctional inhibition of sympathetic neurotransmission. This study therefore provides evi-
dence that, in some targets, the principal action of parasympathetic innervation is mediated indirectly via an inhibitory effect on heterologous excitatory nerves. (Supported by NIH NS23502.) 140 Relationship Between Autonomic Neuropathy, 24 h Blood Pressure and Nephropathy in Normotensive Insulin-Dependent Diabetic Patients V. Spallone 1, S. Gambardella 1, M.R. Maiellol, A. Barini 2, S. Frontoni z and G. Menzinger l
~Endocrinology, Department of Internal Medicine, Tor Vergata University and 2Catholic University, Rome, Italy To evaluate whether the association between autonomic neuropathy and nephropathy in insulin-dependent diabetes mellitus has pathogenetic implications, we simultaneously measured 24-h blood pressure (BP) and urinary albumin excretion rate (UAE) on timed overnight and 2-h periods during the day urine collections. We studied 25 normotensive type I diabetic patients without overt nephropathy, divided into two groups, matched for age, duration of diabetes and HbAb according to the presence of cardiovascular autonomic neuropathy (AN). Mean day (08-22) and night (22-08) systolic (SBP) and diastolic BP (DBP), and UAE did not significantly differ between the groups. Nocturnal percentage decrease (A day-night) in SBP, DBP and UAE were significantly lower in patients with AN compared to those without (SBP: 4.17 + 5 vs. 9.77+4.2%, P<0.004; DBP: 9.85-t-5.7 vs. 15.52+5.5, P<0.01; UAE: -13.74-112.1 vs. 44.94-30.4, P<0.04). A day-night in SBP, DBP, and UAE were inversely related to autonomic score, index of AN degree (r= -0.39, P<0.05; r=-0.55, P<0.01; and r : - 0 . 4 8 , P<0.015, respectively). 2-h day period, day and night UAE were similar in the two groups but were more strongly related, respectively, to mean 2 h (r:0.72, P<0.0001), day (r=0,78, P<0.02) and night SBP (r---0.86, P<0.02) in subjects with AN than in those without (2 h: r = 0.30, P < 0.002; day: r = 0.37, NS; night: r=0.38, NS). AN is associated with reduced nocturnal decrease in BP and in UAE. The stronger relation of UAE to SBP in diabetic patients with AN might suggest that the loss of neural control enhances kidney vulnerability to hemodynamic effects of BP. 141 Neurogenic Orthostatic Hypertension N. Tamura, K. Shimazu, S. Watanabe, K. Itokawa, A. Maeda and K. Hamaguchi
Department of Neurology, Saitama Medical School, Saitama 350-04, Japan