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PROGRESS IN CARDIOVASCULAR DISEASES 1975年第2期18卷 105-122页

作者： RUBIO, R BERNE, RM UNIV VIRGINIA SCH MED DEPT PHYSIOL JORDAN HALL CHARLOTTESVILLE VA 22901 USA

A very schematic summary of possible factors that affect coronary vascular resistance is illustrated in Fig. 11. These factors are mechanical, myogenic, metabolic, and neural.64 Mechanical influence is passive and is essentially determined by the extravascular compression which is important only during systole and particularly in the subendocardial layers of the left ventricular myocardium. With respect to the myogenic factor it is controversial whether it plays a role in adjustments of coronary vascular tone. Metabolic processes are possibly integrated at the level of the myocardial cell PO2 which is the resultant of oxygen supply and need, which in turn depend on the myocardial contractile activity as well as other biochemical processes. A decrease in myocardial PO2 gives rise to the release of the vasodilator metabolite adenosine. Nevertheless, other chemical factors (H+ , K+ , osmolarity) known to be released by the heart (which by themselves are poor and transient coronary vasodilators and whose release does not correspond with changes in coronary resistance) may play a role by modulating the coronary sensitivity to adenosine and other factors.

关键词：腺苷/生理学腺苷一磷酸/代谢冠状动脉循环/药物作用电刺激水解作用乳酸盐类/药理学心肌/酶学心肌/代谢氧氧耗量副交感神经系统/生理学分压灌流磷酸盐类/生理学钾/生理学压力受体肾上腺素能交感神经系统/生理学血管阻力/药物作用血管舒缩系统/生理学动物人类

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Presynaptic muscarinic facilitation of parasympathetic neurotransmission after sympathectomy in the rat choroid

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期294卷 627-632页

作者： Steinle, JJ Smith, PG Univ Kansas Med Ctr Dept Mol & Intergrat Physiol Kansas City KS 66160 USA Univ Kansas Med Ctr RL Smith Mental Retardat Res Ctr Kansas City KS 66160 USA

The effect of sympathectomy on parasympathetic regulation of ocular perfusion was investigated. Uveal blood flow through the vortex veins was measured by laser Doppler flowmetry during electrical stimulation of the superior salivatory nucleus, which activates ocular parasympathetic nerves, in adult rats with intact innervation and 2 days or 6 weeks after excision of the ipsilateral superior cervical ganglion. In all groups, parasympathetic stimulation produced comparable increases in flux, which were abolished by the selective neuronal nitric-oxide synthetase inhibitor, 1-(2-trifluoromethylphenyl) imidazole. Atropine had no effect in control and acutely sympathectomized rats but abolished the flux increase in four of six chronically sympathectomized animals, and 1-(2-trifluoromethylphenyl) imidazole eliminated the residual response. The muscarinic receptor agonist bethanechol did not affect basal flow in control or sympathectomized rats. However, bethanechol enhanced parasympathetically mediated vasodilation, but only in rats studied at 6 weeks after sympathectomy, a finding consistent with the appearance of muscarinic prejunctional facilitation of nitrergic transmission. In chronically sympathectomized rats, the M-2 and M-4 receptor antagonists methoctramine and tropicamide did not affect choroidal flow during parasympathetic activation. However, pirenzepine increased flux, implying the presence of M-1 inhibitory autoreceptors on these nerves. Parasympathetically mediated increased flux was partially blocked by the M-3 antagonist 4-diphenylacetoxy-N-methylpiperdine, and the remaining vasodilation was blocked by atropine. We conclude that parasympathetic prejunctional facilitatory M-3 and probably M-5 receptors adopt a crucial role after chronic sympathectomy in maintaining nitrergic vasodilatory ocular neurotransmission in the face of down-regulated nitric oxide transmitter mechanisms.

关键词：氯贝胆碱/药理学脉络膜/血液供给脉络膜/药物作用脉络膜/神经支配电刺激酶抑制剂/药理学神经节切除术咪唑类/药理学毒蕈碱激动剂/药理学毒蕈碱拮抗剂/药理学一氧化氮/生理学一氧化氮合酶/拮抗剂和抑制剂一氧化氮合酶Ⅰ型副交感神经系统/药物作用副交感神经系统/生理学哌啶类/药理学大鼠 Sprague-Dawley 受体毒蕈碱/分类受体毒蕈碱/生理学受体突触前/生理学局部血流/药物作用局部血流/生理学涎腺/神经支配颈上神经节/生理学颈上神经节/外科学突触传递/药物作用突触传递/生理学时间因素动物女(雌)性大鼠

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A method for determining baroreflex-mediated sympathetic and parasympathetic control of the heart in pregnant and non-pregnant sheep

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第2期515卷 555-566页

作者： Lumbers, ER Yu, ZY Univ New S Wales Sch Physiol & Pharmacol Sydney NSW 2052 Australia

1. The cardiac baroreflex was measured in four non-pregnant and six pregnant ewes before and during beta-adrenoreceptor blockade with propranolol and before and during vagal blockade with atropine. Arterial pressure was raised by phenylephrine and lowered by sodium nitroprusside. The relationships between mean arterial pressure (MAP) and heart rate (HR), between MAP and heart rate variability (HRV) measured as the coefficient of variation (c.v.) of the mean pulse interval (PI), and between MAP and HRV measured by power spectral analysis were determined. 2. The MAP-MR relationship showed that in pregnant ewes the gain of the cardiac baroreflex was reduced when compared with non-pregnant ewes. Threshold and saturation pressures mere higher, maximum achievable HR was lower and there was a decrease in the operating range. 3. V-shaped relationships were obtained between MAP and HRV (measured as the c.v of PI) and between MAP and power spectral density in the frequency range 0.04-0.08 Hz. Using selective autonomic blockade the negative, or downward, slope of the V shape was shown to be a measure of baroreceptor-induced, sympathetically mediated effects on HRV. The upward, or positive, slope of the V shape was a measure of baroreceptor-induced, vagally mediated effects. Similar results were also obtained from the cardiac power spectrum, but it was less sensitive. The MAP at which the two slopes intersected was the same as the resting MAP. 4. In pregnant ewes, the slope of the downward limb of the V-shaped relationship between HRV (when measured as the c.v. of PI) and MAP was less than in non-pregnant ewes. 5. The relationship between MAP and the coefficient of variation of the mean pulse interval can therefore be used to measure the degree to which baroreceptor-induced sympathetic and parasympathetic activity affects the heart. 6. The resting MAP is the pressure at which the net effect of these sympathetic and parasympathetic influences on the heart is at a minimum. Studie

关键词：压力感受器反射/生理学血压/生理学心脏传导系统/生理学心率/生理学方法副交感神经系统/生理学妊娠动物/生理学参考值交感神经系统/生理学动物女(雌)性妊娠

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Purinergic and cholinergic neuro-neuronal transmission underlying reflexes activated by mucosal stimulation in the isolated guinea-pig ileum

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JOURNAL OF PHYSIOLOGY-LONDON 2000年第2期522卷 321-331页

作者： Spencer, NJ Walsh, M Smith, TK Univ Nevada Sch Med Dept Physiol & Cell Biol Reno NV 89557 USA

1. We present evidence that adenosine triphosphate (ATP) plays a major role in excitatory neuro-neuronal transmission in ascending and descending reflex pathways to the longitudinal (LM) and circular muscle (CM). 2. A partitioned bath was used for the pharmacological isolation of a segment of guinea-pig ileum (similar to 6 cm in length), allowing drugs to be selectively applied to an intermediate region between the region where mucosal stimulation was applied and that where mechanical recordings were made. 3. Brush stroking the mucosa (3 strokes) elicited a synchronous contraction of the LM and CM both above (ascending excitation) and below (descending excitation) the site of stimulation. All reflexes were abolished when tetrodotoxin (1 mu M) was applied to the intermediate chamber. 4. Hexamethonium (300 mu M) added to the intermediate chamber abolished the ascending contraction in 15% of oral preparations (from 26 preparations, 18 animals) and the descending contraction in 13% of anal preparations studied (from 53 preparations, 48 animals). In the remaining 85% of oral preparations, hexamethonium usually attenuated the oral contraction of the LM and CM. However, in the remaining 87% of anal preparations, hexamethonium had no effect on the anal contraction of the LM and CM. 5. Oral and anal reflexes that were hexamethonium resistant were either abolished or attenuated by the further addition of the P2 purinergic receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 mu M) or alpha,beta-methylene ATP (50-100 mu M) to the intermediate chamber. 6. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP, 20 mu M) or alpha,beta-methylene ATP (50-100 mu M) stimulated both ascending and descending excitatory pathways, when applied to the intermediate chamber. 7. In conclusion, ascending and descending neuro-neuronal transmission in excitatory nervous pathways to the LM and CM is complex and clearly involves neurotransmitter(s) other than acetylcholin

关键词：乙酰胆碱/药理学腺苷三磷酸/药理学钙/生理学二甲基苯基哌嗪碘化物/药理学六烃季铵/药理学中间神经元/生理学肠黏膜/神经支配肠黏膜/生理学镁/生理学运动神经元/药物作用运动神经元/生理学肌平滑/药物作用肌平滑/神经支配肌平滑/生理学神经通路/生理学神经元/生理学烟碱激动剂/药理学烟碱拮抗剂/药理学副交感神经系统/生理学受体嘌呤能/生理学反射/生理学突触传递/生理学动物豚鼠

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Spinal cholinergic neurons activated during locomotion: Localization and electrophysiological characterization

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JOURNAL OF NEUROPHYSIOLOGY 2000年第6期83卷 3537-3547页

作者： Huang, A Noga, BR Carr, PA Fedirchuk, B Jordan, LM Univ Manitoba Fac Med Dept Physiol Winnipeg MB R3E 3J7 Canada

The objective of the present study was to determine the location of the cholinergic neurons activated in the spinal cord of decerebrate cats during fictive locomotion. Locomotion was induced by stimulation of the mesencephalic locomotor region (MLR). After bouts of locomotion during a 7-9 h period, the animals were perfused and the L-3-S-1 spinal cord segments removed. Cats in the control group were subjected to the same surgical procedures but no locomotor task. The tissues were sectioned and then stained by immunohistochemical methods for detection of the c-fos protein and choline acetyltransferase (ChAT) enzyme. The resultant c-fos labeling in the lumbar spinal cord was similar to that induced by fictive locomotion in the cat. ChAT-positive cells also clearly exhibited fictive locomotion induced c-fos labeling. Double labeling with c-fos and ChAT was observed in cells within ventral lamina VII, VIII, and possibly IX. Most of them were concentrated in the medial portion of lamina VII close to lamina X, similar in location to the partition and central canal cells found by Barber and collaborators. The number of ChAT and c-fos-labeled neurons was increased following fictive locomotion and was greatest in the intermediate gray, compared with dorsal and ventral regions. The results are consistent with the suggestion that cholinergic interneurons in the lumbar spinal cord are involved in the production of fictive locomotion. Cells in the regions positive for double-labeled cells were targeted for electrophysiological study during locomotion, intracellular filling, and subsequent processing for ChAT immunohistochemistry. Three cells identified in this way were vigorously active during locomotion in phase with ipsilateral extension, and they projected to the contralateral side of the spinal cord. Thus a new population of spinal cord cells can be defined: cholinergic partition cells with commissural projections that are active during the extension phase of locomotion.

关键词：轴突/酶学轴突/代谢轴突/生理学胆碱O-乙酰转移酶/代谢电刺激电生理学免疫酶技术免疫组织化学行走/生理学中脑/细胞学中脑/生理学神经元/酶学神经元/代谢神经元/生理学副交感神经系统/细胞学副交感神经系统/代谢副交感神经系统/生理学原癌基因蛋白质c-fos/代谢脊髓/细胞学脊髓/生理学动物猫

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Activation of intrinsic hippocampal theta oscillations by acetylcholine in rat septo-hippocampal cocultures

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第2期519卷 405-413页

作者： Fischer, Y Gähwiler, BH Thompson, SM Univ Zurich Brain Res Inst CH-8057 Zurich Switzerland Univ Maryland Sch Med Dept Physiol Baltimore MD 21201 USA

1. Oscillatory electro-encephalographic activity at theta frequencies (4-15 Hz) can be recorded from the hippocampus in vivo and depends on intact septal projections. The hypothesis that these oscillations are imposed on the hippocampus by rhythmically active septal inputs was tested using dual. intracellular recordings from CA1 and CA3 pyramidal cells in septohippocampal cocultures. 2. Septo-hippocampal cocultures displayed spontaneous oscillatory synaptic activity at theta frequencies. In CA3 cells, EPSP/IPSP sequences predominated, whereas only EPSPs were apparent in CA1 cells. Synaptic potentials in CA3 cells preceded those in CA1 cells by 5-10 ms. 3. Oscillatory synaptic activity was blocked in cocultures by the muscarinic antagonist atropine (0.1 mu M), facilitated but unchanged in frequency upon application of the acetylcholinesterase inhibitor neostigmine (1 mu M), and not seen in hippocampal monocultures. 4. The muscarinic agonist methacholine (5-20 nM) induced oscillatory synaptic activity at 4-15 Hz in hippocampal monocultures, which was identical to that occurring spontaneously in septo-hippocampal cocultures. 5. Synaptic theta activity was observed in cocultures of septal tissue with subdissected hippocampal slices containing area CA3 alone, but not in septo-CA1. cocultures. 6. We conclude that oscillatory synaptic activity at theta frequencies, with similar characteristics to theta activity in vivo, can be generated by the hippocampal network in response to activation of muscarinic receptors by synaptically released acetylcholine from septal afferents. Furthermore, the oscillatory activity is determined by mechanisms intrinsic to the hippocampal circuitry, particularly area CA3. Rhythmic septal input is not required.

关键词：乙酰胆碱/药理学共同培养技术电生理学海马/细胞学海马/药物作用海马/生理学膜电位/生理学微电极神经网/药物作用副交感神经系统/药物作用副交感神经系统/生理学膜片钳术脑中隔/细胞学脑中隔/药物作用脑中隔/生理学突触/药物作用突触/生理学 θ节律/药物作用动物大鼠

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AUTONOMIC RECEPTOR FUNCTIONS IN LOWER URINARY-TRACT - SURVEY OF RECENT EXPERIMENTAL RESULTS

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JOURNAL OF UROLOGY 1975年第2期113卷 180-185页

作者： NERGARDH, A KAROLINSKA SJUKHUSET DEPT CLIN PHARMACOL STOCKHOLM SWEDEN KAROLINSKA SJUKHUSET DEPT PEDIAT UROL STOCKHOLM SWEDEN KAROLINSKA SJUKHUSET DEPT PEDIAT STOCKHOLM SWEDEN

Cholinergic receptor function was identified in the bladder and in its outlet region in different species. Stimulation with acetylcholine contracts muscle segments from man, dog and cat. Acetylcholine stimulation can either increase or decrease flow resistance in the outlet region from the cat in vitro. However, in both cases simultaneous contraction is seen in the longitudinal musculature of the region. The effects on flow resistance are mediated by adrenergic muscle receptors. A probable explanation is that acetylcholine stimulates the ganglia of intramural adrenergic neurons. The type of reaction obtained (increase or decrease) is dependent upon the concentration of released noradrenaline at the neuromuscular junction. Alpha adrenergic receptor function is localized to the bladder base, bladder neck and proximal urethra in man and cat. Alpha adrenergic receptor stimulation of the outlet region leads to a contraction of the internal sphincter mechanism. Beta adrenergic receptor function could be identified in the bladder and the outlet region in man and cat. Beta adrenergic stimulation of this region produces relaxation of the internal sphincter mechanism. The relaxing effect appears to low concentrations of beta adrenergic agonists. In low concentrations adrenaline and noradrenaline relax the outflow region in the cat. High concentrations of these catecholamines contract the same region.

关键词：乙酰胆碱/药理学阿托品/药理学剂量效应关系药物肾上腺素/生理学肌收缩去甲肾上腺素/生理学副交感神经系统/生理学灌流酚妥拉明/药理学苯福林/药理学普萘洛尔/药理学受体肾上腺素能受体胆碱能种特异性交感神经系统/生理学尿道/神经支配膀胱/神经支配膀胱/生理学泌尿道/神经支配动物猫人类男(雄)性

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Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第12期97卷 6826-6831页

作者： Capsoni, S Ugolini, G Comparini, A Ruberti, F Berardi, N Cattaneo, A SISSA Int Sch Adv Studies Program Neurosci I-34014 Trieste Italy CNR Inst Neurophysiol Italian Council Res I-56127 Pisa Italy

Neurotrophin nerve growth factor (NGF) has been suggested to be involved in age-related neurodegenerative diseases, but no transgenic model is currently available to study this concept. We have obtained transgenic mice expressing a neutralizing anti-NGF recombinant antibody, in which the levels of antibodies are three orders of magnitude higher in adult than in newborn mice [F.R., S. C., A.C., E, Di Daniel, J, Franzot, S. Gonfloni, C, Rossi, N. B. & A. C. (2000) J. Neurosci., 20, 2589-2601]. In this paper, we analyze the phenotype of aged anti-NGF transgenic mice and demonstrate that these mice acquire an age-dependent neurodegenerative pathology including amyloid plaques, insoluble and hyperphosphorylated tau, and neurofibrillary tangles in cortical and hippocampal neurons. Aged anti-NGF mice also display extensive neuronal loss throughout the cortex, cholinergic deficit in the basal forebrain, and behavioral deficits. The overall picture is strikingly reminiscent of human Alzheimer's disease. Aged anti-NGF mice represent, to our knowledge, the most comprehensive animal model for this severe neurodegenerative disease. Also, these results demonstrate that, in mice, a deficit in the signaling and/or transport of NGF leads to neurodegeneration.

关键词：衰老阿尔茨海默病/病因学阿尔茨海默病/代谢阿尔茨海默病/病理学抗体/血液脑/病理学胆碱O-乙酰转移酶/代谢认知障碍/病因学 DNA碎片裂记忆障碍/病因学小鼠转基因神经生长因子/免疫学副交感神经系统/生理学磷酰化动物人类小鼠

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REGIONAL BLOOD-FLOW

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ANNUAL REVIEW OF PHYSIOLOGY 1975年第1期37卷 395-414页

作者： LUNDGREN, O JODAL, M UNIV GOTHENBURG DEPT PHYSIOLGOTHENBURGSWEDEN

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Sympathetic inhibition of ascending and descending interneurones during the peristaltic reflex in the isolated guinea-pig distal colon

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第2期519卷 539-550页

作者： Spencer, N McCarron, SL Smith, TK Univ Nevada Sch Med Dept Physiol & Cell Biol Reno NV 89503 USA

1. We investigated the effects of sympathetic nerve stimulation within ascending and descending reflex pathways underlying the peristaltic reflex in the guinea-pig distal colon. 2. A three-chambered partitioned bath was used to divide a segment of distal colon into stimulation, recording and intermediate regions. The effects of lumbar colonic nerves (LCN) could be localized to the intermediate region by surgical lesions of the mesentery and by application of guanethidine (3 mu M) to the stimulation and recording chambers. 3. Brush stroking the mucosa in the anal and oral stimulation chambers elicited a synchronous contraction of the longitudinal muscle (LM) and circular muscle (CM) oral to, and transient relaxation of the LM and CM anal to, the stimulus, respectively. 4. After N-omega-nitro-L-arginine (L-NA;100 mu M) in the oral and intermediate chambers, mucosal stimulation in the oral chamber elicited a prolonged descending inhibitory and excitatory complex in both the LM and CM in the anal recording chamber. This was blocked by hexamethonium (300 mu M), which did not affect the transient relaxation response recorded in control conditions. 5. Stimulation of the LCN (1200 pulses, 20 Hz), delivered to the intermediate region, abolished the oral contraction and the L-NA-induced anal, complex in both the LM and CM, but was without effect on the transient hexamethonium-resistant anal relaxation. These effects of LCN stimulation were reversed by phentolamine (3 mu M) or yohimbine (100 nM), but not propranolol(10 mu M), when added to the intermediate chamber. 6. LCN stimuli (2-20 Hz, 600 mu s pulses) directed to the recording chamber elicited synchronous relaxations in the LM and CM that were unaffected by hexamethonium (300 mu M), but were reduced by yohimbine and usually blocked by the further addition of propranolol(10 mu M). 7. In conclusion, sympathetic nerve stimulation inhibits orally and anally projecting cholinergic interneurones underlying the peristaltic refle

关键词：肾上腺素能α激动剂/药理学肾上腺素能α拮抗剂/药理学自主神经通路/药物作用自主神经通路/生理学结肠/药物作用结肠/神经支配结肠/生理学电刺激中间神经元/药物作用中间神经元/生理学肌收缩/药物作用肌收缩/生理学烟碱激动剂/药理学副交感神经系统/药物作用副交感神经系统/生理学蠕动/药物作用蠕动/生理学反射/药物作用反射/生理学交感神经系统/药物作用交感神经系统/生理学突触传递/药物作用突触传递/生理学动物豚鼠

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