In vivo release by histamine agonists and antagonists of endogenous catecholamines in the cat hypothalamus

Summary The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula with histamine agonists and antagonists and the release of endogenous catecholamines was determined in the superfusate. Hypothalamic superfusion with histamine, 2-methylhistamine (H₁-agonist), dimaprit (H₂-agonist) or metiamide (H₂-antagonist) enhanced the release of the catecholamines dopamine, noradrenaline and adrenaline. The releasing effects of these substances depended on the presence of calcium ions. Superfusion with 2-pyridylethylamine (H₁-agonist) was virtually ineffective, while superfusion with 2-thiazolethylamine (H₁-agonist) enhanced the rate of release of noradrenaline and adrenaline without influencing the release of dopamine. Superfusion with mepyramine (H₁-antagonist) inhibited the release of noradrenaline and adrenaline without affecting the release of dopamine. Hypothalamic superfusion with a concentration of procaine which was equi-anaesthetic to that of mepyramine was ineffective. Ranitidine (H₂-antagonist) did not alter the rates of release of the catecholamines. The releasing effect of histamine was inhibited on hypothalamic superfusion with mepyramine and ranitidine. Ranitidine also inhibited the releasing effects of dimaprit and 2-methylhistamine thus indicating that the releasing action of the latter compound was mainly due to stimulation of H₂-receptors. These data suggest that blockade of H₁-receptors of the posterior hypothalamus reduces the release of noradrenaline and adrenaline, while stimulation of H₁-receptors seems to increase the rates of release of these two catecholamines. Stimulation of H₂-receptors enhances the release of all three catecholamines. Thus, dopaminergic neurones of the hypothalamus seem to possess H₂-receptors, while noradrenergic and adrenergic neurones possess H₁- and H₂-receptors.This work was supported by the Deutsche Forschungsgemeinschaft     

In vivo modulation of the histamine release in the hypothalamus by adrenoreceptor agonists and antagonists

Summary The modulation of the histamine release from histaminergic neurons by noradrenergic neurons was investigated by the push-pull technique.The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial CSF through a push-pull cannula and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with a potassium-rich CSF enhanced the release rate of histamine. Superfusion with the ₂-agonists noradrenaline or clonidine diminished the release rate of histamine. Moreover, clonidine abolished the potassium-induced increase in the histamine release. Superfusion with the ₂-antagonists yohimbine or idazoxan enhanced the release rate of histamine.It is concluded that noradrenaline released from noradrenergic neurons of the hypothalamus modulates the release of histamine from histaminergic neurons by stimulating ₂-adrenoreceptors located on histaminergic nerve terminals.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung Send offprint requests to H. Prast at the above address     

Enhanced nitric oxide release/synthesis in the posterior hypothalamus during nitroglycerin tolerance in rats

We have recently observed that increasing central noradrenergic transmission and sympathomimetic activity is involved with the complex hemodynamic effects during tolerance to nitroglycerin. The present study was to examine the release of nitric oxide (NO) in the posterior hypothalamus during tolerance to depressor responses to nitroglycerin and determine if, during the tolerance, endogenous NO synthesis is induced in the posterior hypothalamus. A microdialysis probe was implanted in the posterior hypothalamus and perfusion fluid was pumped through the probe at 2 microl/min in conscious rats. Tolerance to nitroglycerin was produced by three intravenous (i.v.) injections of 1.3 mg nitroglycerin each within 40 min compared to the same administrations of low dose of the drug, sodium nitroprusside and papaverine. Dialysate samples were collected 1 h before and 1 h each after injections for 8 h. Concentrations of nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total nitrite plus nitrate (NO(x)(-)) were quantified in the samples by using chemiluminescence. The dose-response curve for arterial depressor induced by intravenous injection of the challenge doses of nitroglycerin was markedly shifted to the right at the first hour after nitroglycerin tolerance, lasted 3 to 5 h and reversed at 7 h. The dialysate NO(3)(-) and NO(x)(-) concentrations in the posterior hypothalamus were significantly increased at the first hour following nitroglycerin tolerance but were not altered by low dose of the drug, sodium nitroprusside, and papaverine. Nitroglycerin tolerance predominantly caused an increase in NO(3)(-) release in the posterior hypothalamus with no or small amount of changes in dialysate NO(2)(-) and the response was partially inhibited by pretreatment with N(G)-Propyl-L-arginine (NPLA) (1.0 mg/kg, i.p.), an inhibitor of neuronal NO synthesis. The increase of NO release in the posterior hypothalamus occurred at the first hour, lasted 2 to 3 h and reversed at 5 to 6 h during nitroglycerin tolerance. The results show that systemically administered high dose of nitroglycerin increases NO release in the posterior hypothalamus which matches the time interval of tolerance to arterial depressor response to the drug. Data suggest that there is an enhanced endogenous NO synthesis in the posterior hypothalamus which may affect central sympathetic functions during nitroglycerin tolerance.     

Nitric oxide modulates the release of acetylcholine in the ventral striatum of the freely moving rat

The influence of nitric oxide on acetylcholine release in the ventral striatum was investigated by the push-pull superfusion technique in the conscious, freely moving rat. Superfusion with the nitric oxide donors S-nitroso-N-acetylpenicillamine or with 3-morpholino-sydnonimine caused a pronounced increase in striatal acetylcholine release. This effect was prevented by superfusion with tetrodotoxin. Pre-superfusion with the guanylyl cyclase inhibitor methylene blue abolished the effect of 3-morpholino-sydnonimine. Superfusion of the ventral striatum with the guanylyl cyclase inhibitor LY83583 decreased acetylcholine release by 60% of basal release, whereas the less specific guanylyl cyclase inhibitor methylene blue was ineffective in this respect. Superfusion of the ventral striatum with inhibitors of nitric oxide synthase also led to different effects on basal acetylcholine release. Superfusion with L-N^G-methylarginine did not influence basal acetylcholine release, whereas superfusion with L-N^G-nitroarginine or with L-N^G-nitroarginine methyl ester led to a substantial decrease in acetylcholine output, the latter compound being more effective. The effect of L-N^G-nitroarginine was abolished by simultaneous superfusion with L-arginine.The effects of NO donors and of LY83583 suggest that NO increases acetylcholine release, probably by a cGMP-dependent mechanism. The effectiveness of nitric oxide synthase inhibitors shows that the activity of striatal neurons is under the permanent influence of nitric oxide, that leads, via a direct or indirect mechanism, to continuous enhancement of acetylcholine release.In conclusion, our findings suggest that NO synthesized in the ventral striatum acts as an intercellular messenger which modulates acetylcholine release.     

In vivo modulation of histamine release by autoreceptors and muscarinic acetylcholine receptors in the rat anterior hypothalamus

The modulation of histamine release by histamine and muscarinic acetylcholine receptors was investigated by using the push-pull technique. The anterior hypothalamic area of the conscious, freely moving rat was superfused through the push-pull cannula with CSF or with CSF containing drugs and the release of endogenous histamine was determined in the superfusate.Hypothalamic superfusion with tetrodotoxin (10 mol/1) led to a pronounced and sustained decrease in the histamine release rate. Superfusion with compound 48/80 (100 mg/1) was ineffective. Hypothalamic superfusion with the H₃ agonist (R)--methylhistamine inhibited, while superfusion with the H₃ antagonist thioperamide enhanced the release of histamine. The release of histamine was inhibited on hypothalamic superfusion with the muscarinic receptor agonists carbachol or oxotremorine. Histamine release was enhanced by atropine, and this release-enhancing effect was abolished by oxotremorine. The selective M₁ antagonist pirenzepine (100 mol/I) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10 ol/1), which blocks M₁ and M₃ receptors, also enhanced the release rate of histamine. On the other hand, 50 and 100 moI/I methoctramine (M₂ receptor antagonist) 10 and 100 moI/l p-fluoro-hexahydro-siladifenidol (p-F-HHSiD, a M₃ receptor antagonist) were ineffective.It is concluded that histamine released in the hypothalamus originates predominantly from neurons. The release of histamine is modulated by H₃ autoreceptors. The histamine release is also modulated by cholinergic neurons which modify histamine release from histaminergic neurons by stimulating M₁ muscarinic acetylcholine heteroreceptors probably located on histaminergic neurons.Supported by the Fonds zur Förderung der wissenschaftlichen Forschung Correspondence to: H. Prast at the above address     

Ionic and haemodynamic changes influence the release of the excitatory amino acid glutamate in the posterior hypothalamus

The push-pull technique was used to investigate the release of the excitatory amino acid glutamate in the posterior hypothalamic area of the conscious rat. The hypothalamus was superfused through the pushpull cannula with artificial cerebrospinal fluid (CSF), and the superfusate was collected in time periods of 10 min when ionic conditions in the CSF were changed, or in short periods of 3 min when blood pressure changes were evoked. The mean glutamate release rate was 2.8 + 0.7 pmol/min. Depolarization by hypothalamic superfusion with CSF containing 50 mM K⁺ enhanced the release of glutamate in the presence of Ca²⁺. The K⁺-induced release was attenuated by 40% when the hypothalamus was superfused with Ca²⁺-free CSF. Replacement of Ca²⁺ by Mg²⁺ abolished the K⁺-induced release of glutamate. Hypovolaemia elicited by haemorrhage enhanced the release rate of glutamate. Similarly, a hypotension elicited by i.v. injection of chlorisondamine (3 mg/kg) led to a pronounced and permanent enhancement in glutamate release. The effects of hypovolaemia and chlorisondamine on glutamate release were abolished in aortic denervated rats, indicating that this response is due to a decrease of impulse generation in baroreceptors. A hypovolaemia elicited by blood infusion did not affect the release of glutamate. Similarly, a pronounced pressor response to phenylephrine (15 /kg per minute) infused intravenously for 9 min was ineffective.The results show that the K⁺-induced release of glutamate in the hypothalamus is dependent on the presence of Ca²⁺. The increase in glutamate release rate by hypovolaemia or chlorisondamine suggests that the glutamatergic neurons in the posterior hypothalamic area respond to unloading of aortic baroreceptors and possess a counteracting, hypertensive function.     

Failure of isoprenaline and beta-receptor blocking drugs to modify depressor response and bradycardia induced by electrical stimulation of the anterior hypothalamus of cats

Summary The role of the hypothalamic betaadrenoceptors in the depressor response and bradycardia induced by stimulation of the anterior hypothalamus was studied in cats. In chloralose and urethane anaesthetized cats the anterior hypothalamus was superfused with artifical cerebrospinal fluid through a push-pull cannula. Electrical stimulation of the anterior hypothalamus with the tip of the cannula elicited a fall of systemic blood pressure and a decrease in heart rate. Superfusion of the anterior hypothalamus with isoprenaline did not change the depressor response and bradycardia induced by electrical stimulation of the anterior hypothalamus. Superfusion with atenolol or butoxamine also failed to modify the responses. Superfusion with (±)-propranolol significantly suppressed the responses. However, superfusion with (+)-propranolol suppressed the responses to the same extent. The resting systemic blood pressure and heart rate were not significantly changed by superfusion of the hypothalamus with these drugs. These results suggest that beta-adrenoceptors of the anterior hypothalamus are not involved in the depressor response and bradycardia elicited by hypothalamic stimulation.This work was supported by the Deutsche Forschungsgemeinschaft     

The release of endogenous histamine in distinct brain areas is modified by electrical stimulation

Summary In anaesthetized cats, mamillary bodies, hypothalamic areas and medial amygdaloid nuclei were bilaterally superfused through push-pull cannulae and the effects of the electrical stimulation on the release of endogenous histamine were investigated.Electrical stimulation of the mamillary body increased the release of histamine in the stimulated area, as well as in the contralateral mamillary body. Electrical stimulation of the lateral hypothalamic area enhanced the histamine release in the contralateral hypothalamic area. Stimulation of the posterior hypothalamic area led to a delayed increase in the histamine release in the stimulated area. Stimulation of the medial amygdaloid nucleus reduced the release if histamine in the ipsilateral posterior hypothalamic area, while the histamine release in the contralateral lateral hypothalamic area was enhanced.The results demonstrate that electrical stimulation of distinct brain areas rich in histaminergic neurons may either increase, or decrease the release rate of histamine in the stimulated area and/or in remote brain areas.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung (P5750). Part of the results has been presented at the 26th Spring Meeting of the German Society for Pharmacology and Toxicology, Mainz 1986 Send offprint requests to H. Prast at the above address     

Glial cells participate in histamine inactivation in vivo

The ability of glial cells to take up histamine in vitro suggests that these cells may be involved in histamine inactivation. This prompted us to study the possible interactions between neuronal and glial processes which determine the histamine concentration in the synaptic cleft. In vitro experiments showed that the glial metabolic toxin, fluoroacetate (20 and 40mmol/l) depressed histamine uptake into cultured astroglial cells and dissociated hypothalamic cells of rats. For in vivo experiments, the push-pull superfusion technique was used. In anaesthetized rat, the anterior hypothalamic area was superfused through the push-pull cannula with artificial cerebrospinal fluid (aCSF) or with aCSF which contained fluoroacetate and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with fluoroacetate (20mmol/l) led to a pronounced increase in extracellular histamine. The effect of fluoroacetate was inhibited by 5μmol/l tetrodotoxin. Superfusion with Ca⁺⁺-free, Mg⁺⁺-rich (12mmol/l) aCSF inhibited the basal release rate of histamine. Under these conditions, 20mmol/l fluoroacetate did not modify the level of the amine in the superfusate. These data demonstrate that depression of glial function enhances the concentration of histamine in the extracellular space by slowing down the uptake of the amine into the glial cells. Thus, under in vivo conditions, glial cells are directly involved in the continuous removal of neuronal histamine from the synaptic cleft.     

Release of endogenous acetylcholine in the hypothalamus of conscious rats

Summary The release of endogenous acetylcholine was investigated by the push-pull technique. The posterior hypothalamus of conscious rats was superfused through a push-pull cannula with artificial cerebrospinal fluid (ACSF) which contained 1 mol/l neostigmine. Acetylcholine was determined in the superfusate by high pressure liquid chromatography and electrochemical detection. Hypothalamic superfusion with potassium-rich (100 mmol/l) ACSF led to a pronounced increase in the release rate of acetylcholine. Tetrodotoxin (1 mol/l) almost abolished the basal release of the neurotransmitter. Superfusion of the hypothalamus with atropine (10 or 50 mol/l) led to a concentration-dependent increase, whereas superfusion with oxotremorine (50 mol/l) inhibited the release rate of acetylcholine. It is concluded that acetylcholine released into the superfusate of the hypothalamus originates from cholinergic neurons. Furthermore, the release of acetylcholine seems to be modulated by muscarinic acetylcholine receptors, probably located on cholinergic neurons of the hypothalamus.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung Send offprint requests to H. Prast at the above address     

偏头痛患者血浆的一氧化氮含量的研究

目的:为了探讨NO与偏头痛的关系。方法:采用比色法测定62例偏头痛患者血浆NO的含量。结果:偏头痛患者发作期血浆NO含量明显低于正常对照组,间歇期与正常对照组比较无差异。结论:NO可能参与偏头痛发作。     

Nitric oxide supports atrial function in sepsis: relevance to side effects of inhibitors in shock

The mechanisms underlying myocardial dysfunction in sepsis remain poorly understood. The theoretical benefits of nitric oxide synthase (NOS) inhibition in reversing the haemodynamic changes that characterise septic shock have not been supported by clinical trials, some of which have demonstrated detrimental myocardial effects. We have therefore assessed the effects of endotoxaemia on NOS enzyme expression as well as a number of functional responses of myocardial tissue from rats. Atrial tissue expressed high levels of mRNA for inducible (i) NOS and released increased levels of nitrite after animals were treated with endotoxin. In parallel, the inotropic response stimulated by isoprenaline was reduced in atria from endotoxin-treated animals, an effect that was reversed when endogenous release of NO was maximised. Our results suggest that myocardial contractility is maintained by NO production and that inhibitors may compromise cardiac output; this may explain the deleterious effects of NOS inhibition on cardiac function in clinical trials.     

Nitric oxide and sensory afferent neurones modulate the protective effects of low-dose endotoxin on rat gastric mucosal damage

Pretreatment (1 h) with low doses (5–40 μg/kg i.p.) of Escherichia coli endotoxin dose dependently reduced the gastric mucosal damage induced by a 10 min challenge with 1 ml ethanol (50% and 100%) in conscious rats. Treatment with the nitric oxide synthesis inhibitor, oxide synthesis inhibitor, N^G-nitro- -arginine methyl ester (L-NAME, 5 and 10 mg/kg i.p.), significantly inhibited the protective effects of endotoxin (40 μg/kg i.p.). The actions of L-NAME were reversed by the prior administration of -arginine (100 mg/kg i.p.). The protective effects of endotoxin were not influenced by pretreatment with dexamethasone (5 mg/kg s.c. twice) or indomethacin (5 mg/kg s.c.). However, ablation of sensory afferent neurones by capsaicin pretreatment (20, 30 and 50 mg/kg s.c.) abolished the mucosa protective effects of endotoxin (40 μg/kg). These findings suggest that the protection elicited by low doses of endotoxin against ethanol-induced mucosal damage involves synthesis of nitric oxide and activation of sensory neurones.     

Modulation by dopamine receptors of the histamine release in the rat hypothalamus

Summary The involvement of dopaminergic neurons of the hypothalamus in the modulation of histamine release was studied by the push-pull technique. The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial cerebrospinal fluid (CSF) and the release of histamine was determined radioenzymatically in the superfusate. Agonists and antagonists of dopamine D₁-, D₂- and D₃-receptors were dissolved in CSF and applied to the hypothalamus through the push-pull cannula.Hypothalamic superfusion with the D₁-, D₂- and D₃-receptor agonists dopamine or R(–)-apomorphine enhanced the release rate of histamine. (±) Apomorphine also enhanced the release of histamine, but to a lesser extent than did equimolar concentration of R(–)apomorphine. The D₃-agonist quinpirole inhibited the release of histamine, while the D₁-receptor agonist SKF 82958 [(±)-6-chloro-7,8-dihydroxy-3-allyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] did not virtually influence the release of the neurotransmitter. On the other hand, [–]-sulpiride which predominantly blocks D₂-receptors, decreased histamine release. Hypothalamic superfusion with SKF 83566 [(±)-7-bromo-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], which seems to be a selective antagonist of D₁-receptors, enhanced the release rate of histamine.These findings suggest that dopaminergic neurons of the hypothalamus influence the release of histamine from its neurons in a dual way. D₂-heteroreceptors stimulate the release of histamine, while D₃-heteroreceptors seem to inhibit the release of this neurotransmitter. Both types of dopamine receptors might be located presynaptically on histaminergic neurons. Alternatively, D₃- and D₂-receptors might be located on histaminergic and non-histaminergic neurons, respectively.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung Correspondence to H. Prast at the above address     

Synthesis and release of histamine studied on slices from rat hypothalamus.

In slices from rat hypothalamus, incubated in the presence of 3H-L-histidine (3H-L-His), the aminoacid was rapidly taken up by a saturable process, and partially converted into 3H-histamine (3H-HA). The overall conversion was prevented either by inhibitors of L-histidine decarboxylase or by aromatic aminoacids competing with L-His uptake. The synthesis process exhibited Michaelis--Menten kinetics with an affinity of the aminoacid not different from that for the decarboxylase in homogenates; however the Vmax in homogenates was more than 10 times higher than in slices. Depolarization of the slices by 50 mM potassium resulted in: (a) a calcium-dependent release of 3H-HA which was more marked than that previously reported for endogenous HA, (b) a significant acceleration in the rate of 3H-HA synthesis, which was characterized by an unchanged Km but a significantly elevated Vmax. The regulation of HA synthesis did not appear to depend on end-product inhibition since it was not midified by the addition of exogenous HA. The release of 3H-HA was followed by the accumulation of 3H-methylhistamine, which was enhanced by a monoamine oxidase inhibitor. Aminoguanidine, a diamine oxidase inhibitor, had no effect on catabolism. The involvement of mast-cells in the storage of a fraction of endogenous HA in hypothalamic slices was assessed by the significant releasing effect of compound 48/80. Hence, the data support the existence of two distinct HA stores in the brain: depolarization relases the amine and increases its synthesis, probably in neurones, whereas compound 48/80 releases it from a slowly turning-over store, probably in mast-cells.     

Nitric oxide in the nucleus accumbens is involved in retrieval of inhibitory avoidance memory by nicotine

In the present study, the possible effect of nitric oxide agents injected into the nucleus accumbens (NAc) in the presence or absence of nicotine on morphine state-dependent memory in adult male Wistar rats was investigated. As a model of memory, a step-through type inhibitory avoidance task was used. Post-training injection of morphine (4 and 6 mg/kg) dose dependently induced the impairment of memory retention. Administration of morphine (4 and 6 mg/kg) before retention induced state-dependent retrieval of the memory acquired under post-training morphine (6 mg/kg) influence. Injection of nicotine before retention (0.25 and 0.5 mg/kg) alone and nicotine (0.1, 0.25 and 0.5 mg/kg) plus an ineffective dose of morphine (2 mg/kg) reversed the post-training morphine-induced memory impairment. The amnesia elicited by morphine (6 mg/kg) was also prevented by pre-retention intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, l-NAME (0.24 μg/rat, intra-NAc). Interestingly, an ineffective dose of nicotine (0.1 mg/kg) in combination with low doses of l-NAME (0.06 and 0.12 μg/rat, intra-NAc) synergistically improved memory performance impaired by morphine given after training. It is important to note that intra-NAc administration of l-NAME before retention impaired memory retrieval by itself. In contrast, pre-retention administration of l-arginine, a nitric oxide (NO) precursor (0.25 and 0.5 μg/rat, intra-NAc), which had no effect alone, prevented the nicotine reversal of morphine effect on memory. The results suggest a possible role for nitric oxide of nucleus accumbens in the improving effect of nicotine on the morphine-induced amnesia and morphine state-dependent memory.     

Physiological release of nitric oxide is dependent on the level of vascular tone

The presser effect of N^G-methyl-L-arginine (NMA) was tested in urethane-anesthetized rats which were untreated (control) or devoid of sympathetic tone. In contrast with controls, the NMA response was attenuated by pithing or ganglionic blockade. In pithed rats, the induction of moderate or intense vasoconstriction with constant phenylephrine infusion restored or augmented, respectively, the NMA pressor response. Our data suggest that vascular tone may physiologically regulate the release of nitric oxide in vivo.     

Pre-synaptic histamine H3 receptors regulate glutamate, but not GABA release in rat thalamus

We have investigated the presence of histamine H(3) receptors (H(3)Rs) on rat thalamic isolated nerve terminals (synaptosomes) and the effect of their activation on glutamate and GABA release. N-alpha-[methyl-(3)H]histamine ([(3)H]-NMHA) bound specifically to synaptosomal membranes with dissociation constant (K(d)) 0.78+/-0.20 nM and maximum binding (B(max)) 141+/-12fmol/mg protein. Inhibition of [(3)H]-NMHA binding by histamine and the H(3)R agonist immepip fit better to a two-site model, whereas for the H(3)R antagonist clobenpropit the best fit was to the one-site model. GTPgammaS (30 microM) decreased [(3)H]-NMHA binding by 55+/-4% and made the histamine inhibition fit better to the one-site model. Immepip (30 nM) induced a modest, but significant increase (113+/-2% of basal) in [(35)S]-GTPgammaS binding to synaptosomal membranes, an effect prevented by clobenpropit (1 microM) and by pre-treatment with pertussis toxin. In thalamus synaptosomes depolarisation-induced, Ca(2+)-dependent glutamate release was inhibited by histamine (1 microM, 25+/-4% inhibition) and immepip (30 nM, 38+/-5% reduction). These effects were reversed by clobenpropit (1microM). Conversely, immepip (up to 1 microM) had no effect on depolarisation-evoked [(3)H]-GABA release. Extracellular synaptic responses were recorded in the thalamus ventrobasal complex by stimulating corticothalamic afferents. H(3)R activation reduced by 38+/-7% the glutamate receptor-mediated field potentials (FPs), but increased the FP2/FP1 ratio (from 0.86+/-0.03 to 1.38+/-0.05) in a paired-pulse paradigm. Taken together, our results confirm the presence of H(3)Rs on thalamic nerve terminals and show that their activation modulates pre-synaptically glutamatergic, but not GABAergic neurotransmission.     

雄激素对大鼠主动脉一氧化氮合酶/一氧化氮体系的调节

目的：研究雄激素对大鼠主动脉一氧化氮合酶／一氧化氮(NOS／NO)体系的影响，以探讨雄激素对心血管系统的作用。方法：将30只雄性大鼠随机分为三个组，每组10只，去卵巢组(A组)、去卵巢 雄激素组(B组)、假手术组(C组)。正常饮食2个月后处死大鼠，测血清雄激素、主动脉匀浆一氧化氮合酶活性及一氧化氮含量。结果：同假手术组相比。去势大鼠主动脉匀浆NOS活性及NO含量显著降低，在补充适量的雄激素后．主动脉匀浆NOS活性及NO含量显著上升。结论：雄激素可以调节大鼠动脉内一氧化氮合酶／一氧化氮体系，可能是其调节血管张力的作用机制。