Effect of Huanglian Jiedutang on Learning and Memory Ability and Cholinergic System in AD Rats Induced by Aβ1-42 / 中国实验方剂学杂志

Objective:To investigate the effects of Huanglian Jiedutang on learning and memory ability and the cholinergic system in Alzheimer's disease（AD） rats induced by amyloid <italic>β</italic>-protein（A<italic>β</italic>）_1-42. Method:Sixty male SD rats were divided into normal group， model group， huperzine A group （2.1×10^-5 g·kg^-1）， high-， medium- and low dose of Huanglian Jiedutang groups （6，3，1.5 g·kg^-1）. AD rat model was replicated by hippocampal injection of A<italic>β</italic>_1-42. After 4 weeks of treatment， Morris water maze test was performed. Hematoxylineosin （HE） staining was used to observe the pathological changes of rat hippocampus. Sampling blood from abdominal aorta was taken. Acetylcholine （ACh）， acetylcholinesterase （AchE） and choline acetyltransferase （ChAT） in serum and hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of hippocampal <italic>α</italic>7 nicotinic acetylcholine receptor （<italic>α</italic>7nAChR） protein was detected by Western blot. The expression of hippocampal <italic>α</italic>7nAChR mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， there were obvious pathological changes in the model group，such as neuron necrosis in the cerebral cortex，pyramidal cell or granular cell necrosis in the hippocampus，disorder of arrangement and inflammatory cell infiltration，prolonged escape latency，decreased escape platform times，decreased residence time in the effective area and swimming path in the effective area （<italic>P<</italic>0.05，<italic>P<</italic>0.01）. The contents of <italic>α</italic>7nAChR mRNA，ACh，AchE，ChAT，<italic>α</italic>7nAChR in the hippocampus decreased （<italic>P<</italic>0.01）. Compared with the model group，the escape latency of the middle dose group was shorter （<italic>P<</italic>0.05）， the escape platform times，the swimming path in the effective area and the residence time in the effective area increased （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， the contents of serum ACh，ChAT， hippocampal AchE，ChAT and <italic>α</italic>7nAChR increased （<italic>P<</italic>0.05，）. The expression of hippocampal <italic>α</italic>7nAChR protein significantly increased （<italic>P<</italic>0.01）， the residence time of effective area in high dose group was prolonged （<italic>P<</italic>0.01）， the times of escape platform increased，and the contents of serum ACh，ChAT and hippocampal ACh，AchE，<italic>α</italic>7nAChR protein and <italic>α</italic>7nAChR mRNA increased （<italic>P<</italic>0.05）. Conclusion:Huanglian Jiedutang can significantly improve the learning and memory ability of AD rats induced by A<italic>β</italic>_1-42，and its mechanism may be related to the improvement of cholinergic system damage and enhancement of cholinergic system function induced by A<italic>β</italic>_1-42.

Protective effect of CD73 inhibitor α, ß-methylene ADP against amyloid-ß-induced cognitive impairment by inhibiting adenosine production in hippocampus

BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. RESULTS: We found that acute administration of Aß1­42 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß1­42-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. CONCLUSIONS: In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß1­42 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.

Effect of Tonifying Spleen and Stomach Yuanqi Prescriptions on morphology and function of hippocampus and cortical cholinergic system in SAMP8 mice / 中草药

Objective: To study the effect of Tonifying Spleen and Stomach Yuanqi Prescriptions including ginseng, Dabuyuan Decoction and Xixin Decoction on spatial learning and memory ability, hippocampal morphological function and cortical cholinergic system in rapidly aging dementia model mice (SAMP8), and investigate the possible mechanism on treating Alzheimer's disease. Methods: Male SAMP8 mice aged three months were randomly divided into model group, donepezil group, ginseng group, Xixin Decoction group and Dabuyuan Decoction group. Male anti-aging mice (SAMR1) were used as control group. In addition to control 3 months). The spatial learning and memory ability of mice was observed by Morris water maze test; The synaptic ultrastructure of hippocampal CA3 region was observed by transmission electron microscope; The density of neurons in CA1 area and the level of Aβ in brain tissue were detected by immunohistochemistry; The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus were detected by biochemical method. Results: The average escape latency of mice treated with Tonifying Spleen and Stomach Yuanqi Prescriptions was decreased, the swimming time and the number of passing through the platform were increased significantly (P < 0.05, 0.01). The number of Aβ positive cells were significantly decreased (P < 0.05, 0.01), the density of NueN positive cells had no significant difference. The level of CHAT activity was increased (P < 0.05, 0.01), and the level of AChE activity was decreased (P < 0.05). Conclusion: The effect of Tonifying Spleen and Stomach Yuanqi prescriptions improve the spatial recognition and learning and memory abilities in SAMP8 mice, of which mechanism may be related to affect the synaptic structure of hippocampus, promote the repair of hippocampal neurons, reduce the expression of Aβ in mouse brain, and regulate the cholinergic system in cortex.

Acetylcholinesterase activity and total antioxidant levels in dogs with mammary tumors before and after surgical removal / Actividad de acetilcolinesterasa y niveles totales de antioxidantes en perros con tumores de mama antes y después de la extirpación quirúrgica

ABSTRACT Objective. The aim of this study was to evaluate AChE activity in total blood and the FRAP levels in samples from dogs with mammary tumors before and after surgery, as well as the relationship between these variables with immunohistochemical markers of tumor (E-caderina, ki-67, COX-2). Materials and methods. In this study, 13 dogs with mammary tumors were divided into two groups (A and B). The group A was formed by dogs with tumors smaller than 3 cm of diameter, and the group B was formed by dogs with tumor of 3 cm of diameter or larger. The AChE activity and FRAP levels were evaluated before and after surgery and the immunohistochemistry were performed at the tumors. Results. The AChE activity was significantly increased (p<0.05) in dogs with mammary cancer compared to control animals, and neither surgery or tumor size affected the AChE activity (p>0.05). FRAP levels before surgery were significantly lower (p<0.05) compared to control animals. Also, FRAP levels increased significantly after surgery in animals of the group A compared to data before surgery, a fact not observed in dogs from the group B. E-cadherin showed low significant positive correlation with FRAP levels (r=0.37, p-value=0.05); COX-2 showed a moderate significant positive correlation to FRAP (r=0.55, p-value<0.05); and COX-2 showed a low significant positive correlation to AChE (r=0.32, p-value=0.01). Conclusions. AChE and antioxidant levels are modified in dogs with mammary cancer. These variables are involved in various physiological functions, and thus, they might be related to disease pathogenesis.

RESUMEN Objetivo. Evaluar la actividad de la AChE en sangre total y los niveles de FRAP en muestras de perros con tumores mamarios antes y después de la cirugía, así como la relación entre estas variables con marcadores inmunohistoquímicos de tumores (E-caderina, ki-67 , COX - 2). Materiales y métodos. En este estudio, 13 perros con tumores mamarios se dividieron en dos grupos (A y B). El grupo A estaba formado por perros con tumores menores de 3 cm de diámetro y el grupo B estaba formado por perros con tumor de 3 cm de diámetro o más. La actividad de AChE y los niveles de FRAP se evaluaron antes y después de la cirugía y la inmunohistoquímica se realizó en los tumores. Resultados. La actividad de la AChE aumentó significativamente (p<0.05) en perros con cáncer mamario en comparación con los animales control, y ni la cirugía ni el tamaño tumoral afectaron la actividad de la AChE (p>0.05). Los niveles de FRAP antes de la cirugía fueron significativamente más bajos (p<0.05) en comparación con los animales control. Además, los niveles de FRAP aumentaron significativamente después de la cirugía en animales del grupo A en comparación con los datos antes de la cirugía, hecho que no se observó en perros del grupo B. La E-cadherina mostró correlación positiva baja con los niveles de FRAP (r = 0.37, valor p=0.05); COX-2 mostró una moderada correlación positiva significativa con FRAP (r = 0.55, p-valor<0.05); Y la COX-2 mostró una correlación positiva de baja significación con la AChE (r = 0.32, p-valor = 0.01). Conclusiones. AChE y los niveles de antioxidantes se modifican en perros con cáncer de mama. Estas variables están implicadas en diversas funciones fisiológicas, y por lo tanto, pueden estar relacionadas con la patogénesis de la enfermedad.

Liver metabolomics study of effects of Glycyrrhizae Radix et Rhizoma extracts on D-galactose-induced rats / 中草药

Objective To study the effects of Glycyrrhizae Radix et Rhizoma extracts on aging rats induced by D-galactose and explore its mechanism. Methods The rats were randomly divided into five groups, including control group, D-galactose group, and D-galactose combined with licorice extract of low, medium, and high dose group (respectively 1, 5, and 10 g/kg). The model rats were induced by injecting intraperitoneal D-galactose (300 mg/kg) for five weeks and the control group was received analogous saline. In the final week, the rats were executed and the liver tissue of each rat was used hematoxylin-eosin staining (HE staining) to observe the damage. The AST and ALT of serum were used to quantify the damage degree of liver. And then the MDA content, superoxide dismutase, glutathione peroxidase, and acetylcholinesterase activity in liver tissue were determined. Results The result of HE staining and the activity of AST and ALT showed that Glycyrrhizae Radix et Rhizoma extracts (1 g/kg) can significantly improve the damage of liver induced by D-galactose. Licorice extracts also can significantly reduce liver tissue of aged rats with MDA (P < 0.05) content and AChE activity, and increase SOD and GSH-Px activity. These results showed that Glycyrrhizae Radix et Rhizoma extracts (1 g/kg) with significant antioxidant and regulation of cholinergic system function. In order to further explore the mechanism of action of its effects, the liver tissue was analyzed by NMR metabonomics technique. A total of 13 potential biomarkers were found, which mainly involved in four metabolic pathways. Conclusion Metabonomics provides a scientific method for the further study on the mechanism of aging induced by D-galactose and the delayed aging of Glycyrrhizae Radix et Rhizoma extracts.

Expression of non-neuronal cholinergic system in maxilla of rat in vivo

BACKGROUND: Acetylcholine (ACh) is known to be a key neurotransmitter in the central and peripheral nervous systems, which is also produced in a variety of non-neuronal tissues and cell. The existence of ACh in maxilla in vivo and potential regulation role for osteogenesis need further study. RESULTS: Components of the cholinergic system (ACh, esterase, choline acetyltransferase, high-affinity choline uptake, n- and mAChRs) were determined in maxilla of rat in vivo, by means of Real-Time PCR and immunohistochemistry. Results showed RNA for CarAT, carnitine/acylcarnitine translocase member 20 (Slc25a20), VAChT, OCTN2, OCT1, OCT3, organic cation transporter member 4 (Slc22a4), AChE, BChE, nAChR subunits α1, α2, α3, α5, α7, α10, ß1, ß2, ß4, γ and mAChR subunits M1, M2, M3, M4, M5 were detected in rat's maxilla. RNA of VAChT, AChE, nAChR subunits α2, ß1, ß4 and mAChR subunits M4 had abundant expression (2(-ΔCt) > 0.03). Immunohistochemical staining was conducted for ACh, VAChT, nAChRα7 and AChE. ACh was expressed in mesenchymal cells, chondroblast, bone and cartilage matrix and bone marrow cells, The VAChT expression was very extensively while ACh receptor α7 was strongly expressed in newly formed bone matrix of endochondral and bone marrow ossification, AchE was found only in mesenchymal stem cells, cartilage and bone marrow cells. CONCLUSIONS: ACh might exert its effect on the endochondral and bone marrow ossification, and bone matrix mineralization in maxilla.

Learning and memory promoting effects of crude garlic extract.

Chronic administration of aged garlic extract has been shown to prevent memory impairment in mice. Acute and chronic (21 days) effects of marketed formulation of crude garlic extract (Lasuna) were evaluated on learning and memory in mice using step down latency (SDL) by passive avoidance response and transfer latency (TL) using elevated plus maze. Scopolamine (0.4 mg/kg, ip) was used to induce amnesia in mice and piracetam (200 mg/kg, ip) served as positive control. In the acute study, Lasuna (65 mg/kg, po) partially reversed the scopolamine-induced amnesia but failed to improve learning and memory in untreated animals. Chronic administration of Lasuna (40 mg/kg/day for 21 days) significantly improved learning both in control and scopolamine induced amnesic animals. Influence of Lasuna on central cholinergic activity and its antioxidant properties were also studied by estimating the cortical acetylcholinesterase (AchE) activity and reduced glutathione (GSH) levels respectively. Chronic administration of Lasuna inhibited AchE, while increasing GSH levels. Thus the results indicate that long-term administration of crude garlic extract may improve learning and memory in mice while the underlying mechanism of action may be attributed to the anti-AchE activity and anti-oxidant property of garlic.

Neurotoxicidade de pesticidas organofosforados durante o desenvolvimento: alterações bioquímicas e comportamentais / Neurotoxicity of organophosphorus pesticides during development: behavioral and biochemical changes

Pesticidas organofosforados são amplamente usados e seu uso constitui um grave problema de saúde pública. A ação clássica destes compostos é a inibição irreversível da acetilcolinesterase, promovendo acúmulo de acetilcolina nas sinapses e hiperestimulação colinérgica. No entanto, as consequências da exposição a baixas doses podem se estender a outros mecanismos de ação e sistemas neurotransmissores. Considerando que crianças constituem um grupo particularmente vulnerável aos efeitos de pesticidas, neste trabalho investigamos os efeitos da exposição aos organofosforados metamidofós (MET) e clorpirifós (CPF) durante o desenvolvimento sobre os sistemas colinérgico e serotoninérgico e sobre o comportamento de camundongos. Para isso, camundongos suíços foram expostos a injeções subcutâneas de MET, clorpirifós ou veículo do terceiro (PN3) ao nono (PN9) dias de vida pós-natal. As doses de exposição foram previamente escolhidas através da construção de uma curva dose-resposta que identificou como mais adequadas para este estudo as doses de 1mg/kg de MET e 3mg/kg de CPF, as quais promoveram em torno de 20% de inibição da acetilcolinesterase. Em PN10, parte dos animais foi sacrificada e foram avaliados os sistemas colinérgico e serotoninérgico no tronco encefálico e córtex cerebral. De PN60 a PN63, os animais foram submetidos a uma bateria de testes comportamentais. Em seguida, estes animais também foram sacrificados tendo sido avaliados os sistemas colinérgico e serotoninérgico. Em PN10, MET e CPF causaram alterações que sugerem aumento da atividade colinérgica respectivamente no tronco e córtex em fêmeas. No sistema serotoninérgico, apenas CPF promoveu alterações, aumentando a ligação ao receptor 5HT1A e transportador 5HT em fêmeas e diminuindo na ligação ao 5HT2. Em PN63, a atividade da acetilcolinesterase foi reestabelecida em todos os grupos. Ainda assim, MET diminuiu a atividade da colina acetiltransferase no córtex e a ligação ao transportador colinérgico.

Organophosphate pesticides are widely used and its use consist on a severe public health problem. The classic effect of these compounds involve irreversible inhibition of the enzyme acetylcholinesterase, causing an accumulation of acetylcholine at cholinergic synapses and, consequently, cholinergic hyperstimulation. However, when the doses of exposure are low, other the mechanisms of action may play a role and other neurotransmitter systems may be affected. Considering that children are particularly vulnerable to effects of these compounds, in this study we investigated the effects of methamidophos and chlorpyrifos organophosphate exposure during development on cholinergic and serotonergic systems and behavior. For this purpose, Swiss mice received subcutaneous injections of methamidophos or chlorpyrifos, or vehicle from the third to the nineth postnatal day (PN3 - PN9). Initially, a dose-response study was performed and the doses of 1mg/kg methamidophos and 3mg/kg chlorphrifos, which promoted 20% inhibition of acetylcholinesterase activity in brain were chosen to be used in the next set of experiments. At PN10, one day after exposure, a group of animals was sacrificed and the brainstem and cortex collected and stored to further analysis of cholinergic and serotonergic systems. From PN60 to PN63 the animals were submitted to behavioral tests in order to evaluate: anxiety, locomotor activity, decision making, depressive-like behavior and learning/memory. After the last test, the animals were sacrificed and the brainstem and cortex collected and stored to further analysis of cholinergic and serotonergic systems. At PN10, methamidophos and chlorpyrifos promoted alterations that suggest an increase of cholinergic activity respectively on the brainstem and cortex of females. As for the serotonergic system: only chlorpyrifos elicited alterations: There were increases in 5HT1A receptor and 5HT transporter binding in females and a decrease in 5HT2 receptor binding.

Expression and Function Analysis of Cholinergic Components nAChRα7 in Preadipocytes / 中国生物化学与分子生物学报

The non-neuronal cholinergic system, widely exists in prokaryotic, eukarytic, and even plant cells, however, it has not been investigated in preadipocytes and adipocytes. To search for evidence its existence in preadipocytes and adipocytes, the nicotinic acetylcholine receptor (nAChR) α7 subunit, acetyicholinesterase (ACHE) and choline acetyltransferase (CHAT) in 3T3-L1 cells were examined using immunohistochemical staining and Western blotting. The choline-regulated visfatin expression in 3T3-L1 preadipocytes was also tested by reverse transcriptase-PCR. Incubation with methyilycaconitine (10-6 to 10-4mol/L) for 12, 24 and 36 hours dose-dependently increased visfatin expression from 1.3- to 1.55-folds (P <0.01) with maximal induction at 24 hours with 10-4mol/L methyllycaconitine. Nicotine treatments (10-6 to 10-4 mol/L) for 12, 24 and 36 hours decreased visfatin expression; choline chloride (10-4 mol/L))suppressed visfatin expression in 3T3-L1 preadipocytes at 36 hours by 1.64 to 2.03 fold (P < 0.05) which was more effective as compared with nicotine. It was concluded that α7 nAChR was expressed in 3T3-L1 preadipocytes and involved in visfatin expression.

An innate cholinergic system and its regulation in mature dendritic cell / 中国病理生理杂志

AIM: To investigate whether there was nicotinic acetylcholine receptor subunit α 7 (nAChR α 7 ), choline acetyltransferase(ChAT), acetylcholinesterase(AChE) expression and its regulation in mature dendritic cells (DCs). METHODS: Bone marrow(BM) -derived DCs from healthy BALB/c mice were incubated with rmGM -CSF and rmIL-4, and stimulated to mature with LPS. Meanwhile, light microscope and flow cytometry were used to identify DCs, as well as immunocytochemistry, immunofluorescence, flow cytometry and RT - PCR methods were used to dectect expression of nAChR α 7, ChAT and AChE. Flow cytometry was also used to analyze nAChR α 7 expression with mecamylamine (MEC) in 12 h. RESULTS: Both protein and mRNA expression of cholinergic system nAChR α 7, ChAT and AChE were found in mature DCs. Furthermore, nAChR α 7 distributed principally in cell membrane, while ChAT and AChE in cytoplasm. Protein expression of AChE was stronger as compared with ChAT ( P ＜ 0. 05), and there was a trend toward increasing as compared with nAChR α 7. And then, the expression of nAChR α 7 was down regulated by MEC as compared with the group without MEC stimulation(P ＜ 0. 05 ). CONCLUSION: An innate cholinergic system was in mature DCs, which was affected by extrinsic factor ( i. e. , MEC). And it may be involved in anti - inflammation immune adjustion of cholinergic closed - circuit.

Advance in research on cholinergic theory of Alzheimers disease / 中国药理学通报

It is generally agreed that the central cholinergic system plays an important role in learning and memory processes. Alzheimers disease (AD), the most common cause of dementia, is a devastating illness characterized by progressive cognitive deterioration. The learning and cognitive deficits observed in AD patients are hypothesized to be partly caused by central cholinergic system dysfunction. There exists a malicious cycle in the pathologic course of AD, that is, the impairment of central cholinergic transmission could increase the amount of A? in the brain, and the increase of A? could also impair the efficacy of the cholinergic transmission.

Effects of Dihuang Yizhi Extract on the behavior and cholinergic system in the rats with Alzheimer's disease / 中成药

AIM: To investigate the effects of Dihuang Yizhi Extract(DHYZE) on learning-memory ability and the central cholinergic system of the rats with Alzheimer's disease(AD) and to explore the possible mechanism of action. METHODS: Aggregated A?25-35 was injected into the right hippocampus of the rats to make experimental rat model of AD.The behavioral abnormalities were investigated by shuttle box.The contents of acetylcholine(Ach)、cholinesterase(ChE) activity、cyclic AMP response element-binding protein(CREB) and phosphorylated CREB serine 133(pCREB Ser133) in hippocampus were measured. RESULTS: DHYZE could markedly improve the function of learning and memory of rats in AD model in a dose-dependent manner.The contents of Ach and AchE activity in hippocampaus increased obviously in DHYZE medium dose group and high dose group compared with AD group.Such promotion was dose-dependent.The contents of pCREB Ser133 in hippocampaus increased obviously in DHYZE high dose group compared with AD group. CONCLUSION: The results indicate DHYZE could improve the ability of spatial learning and memory in AD rats.The mechanism might be associated with improving the impairment of the central cholinergic neurons induced by A?25-35 and activating CREB signal pathway in hippocampus of AD rats.

Research progress in improving brain function by Anemarrhena asphodeloides Bge and its effective components / 中国药理学通报

Saponin and sapogenin are main components in chinese medicine Anemarrhena asphodeloides Bge.Modern research has shown that Anemarrhena asphodeloides Bge and its effective components could markedly enhance the ability of learning and memory in dementia animals,as well as improve the descent of brain function.The effect was related with many factors such as inhancing the cholinergic receptor(M,N),improving the activity of ChAT and inhibiting the activity of AChE,regulating the balance of ? receptor-cAMP and M receptor-cGMP,improving the metabolite of free radicals in model animal brains and so on.

Sequence analysis of muscarinic receptors M1, M3 and M5 expression by cultured rat astrocyte cells / 中国药理学通报

Aim To clone the muscarinic receptors M1, M3 and M5 sequences of astrocyte cells,and compare the gene and protein sequences with those of neurons. Methods Specific primers were designed to clone the M1, M3 and M5 sequences of astrocyte cells by RT-PCR according to those of neurons,then sequenced the sequences. Result By comparing the M1, M3 and M5 sequences expression by astrocyte cells with those by neurons and we found four, eight,and one different bases and one, four and one different amino acids in M1, M3 and M5 between astrocyte cells and neurons respectively. Conclusions The gene and protein sequence differences are evident in M1, M3 and M5 between astrocyte cells and neurons.

Relationship between Hippocampal Theta Rhythm and Pressor Effect during Noxious Stimulus in Rabbits / 第三军医大学学报

It is known that hippocampal EEG and blood pressure can be influenced bynoxious stimuli, but the relationship between the hippocampal theta rhythm andthe pressor effect has not been made clear. In this article, the relationship betweennoxious stimulus and the central cholinergic activity after the hippocampal thetarhythm was inhibited or blocked was studied.There was an obvious correlation between the duration of the hippocampal theta rhythm and that of the pressor effect when an noxious stimulus was given. But the duration and reaction of pressor effect were inhibited if 100 ?g of atropine was injected into one of the lateral ventricles and it was strengthened if 100 ?g of mascarine was injected intraventricularly. After the clectrocoagulation of the medial septum, the hippocampal theta rhythm could not be evoked by noxious stimulus and the pressor effect was also obviously inhibited.These results seem to indicate that the hippocampus plays a role in the regulation of blood pressure, the mechanism of which may be mediated through the central cholinergic system.