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1.
The uptake of [ 3H]ACHC and [ 3H]GABA into cultured neurons and astrocytes was studied. [ 3H]ACHC uptake was less efficient than that of GABA in both cell types and Km values for ACHC uptake into neurons and astrocytes were 40.3 μM and 210.8 μM, respectively. The corresponding V max values were 0.321 and 0.405 nmol·min −1·mg −1 cell protein, respectively. Kinetic studies of the effects of GABA on ACHC uptake and vice versa showed that GABA is a linear competitive inhibitor of ACHC uptake in both cell types with a Ki value of 15 μM. On the other hand, ACHC turned out to be a complex inhibitor of astrocytic GABA uptake being competitive at lower concentrations and non-competitive at higher concentrations. ACHC inhibited GABA uptake into neurons competitively with a Ki of 69 μM. It is concluded that ACHC acts primarily on neuronal GABA uptake sites but its uptake is much more complicated than hitherto anticipated. 相似文献
2.
Background: Thrombocytopenia is recognized as one of the most common complications when the patients with severe heart failure are treated with cardiotropic phosphodiesterase (PDE)-3 inhibitors. To understand the mechanism of the onset of this complication, we focused on the effects of various PDE-3 inhibitors and its stable metabolite of acetylamrinone on platelet aggregation occurring under physiological shear stress conditions. Method: Blood specimens were obtained from eight apparently healthy adult donors. Platelet-rich plasma was separated after anticoagulation by citrate. The effects of PDE-3 inhibitors of amrinone and olprinone, as well as the stable metabolite of the former of acetylamrinone, on platelet aggregation induced by its exposure to a shear rate of 1200 and 10,800 s −1 were determined by optically modified cone-plate viscometer. Results: Both olprinone and amrinone inhibited platelet aggregation at 10,800 s −1 in a dose-dependent manner with the IC 50 value of 14±1 and 61±8 μM (mean±S.D.), respectively, while amrinone significantly inhibited platelet aggregation at 1200 s −1 only at highest concentration tested (100 μM). Contrary to the effects shown with PDE-3 inhibitors, acetylamrinone did not inhibit platelet aggregation at all. Moreover, it even enhanced the aggregation at 1200 s −1 when used with 5 μM. Conclusions: Our results demonstrate possible contribution of the enhancing effects of acetylamrinone on platelet aggregation occurring under blood flow conditions, which reduced the platelet count when occurring in real circulation, to the higher incidence of thrombocytopenia in patients treated with amrinone. 相似文献
3.
The electrogenic Na/K pump current (Ip) was studied in the dissociated neostriatal neurons of the rat by using the nystatin-perforated patch recording mode. The Ip was activated by external K + in a concentration-dependent manner with an EC 50 of 0.7 mM at a holding potential ( VH) of −40 mV. Other monovalent cations also caused Ip and the order of potency was Tl +>K +, Rb +>NH 4+, Cs +>>>Li +. The Ip decreased with membrane hyperpolarization in an external solution containing 150 mM Na +, while the Ip did not show such voltage dependency without external Na +. Ouabain showed a steady-state inhibition of Ip in a concentration- and temperature-dependent manner at a VH of −40 mV. The IC 50 values at 20 and 30°C were 7.1×10 −6 and 1.3×10 −6 M, respectively. The decay of Ip after adding ouabain well fitted with a single exponential function. At a VH of −40 Mv, the association ( k+1) and dissociation ( k−1) rate constants estimated from the time constant of the current decay at 20°C were 4.0×10 2 s −1 M −1 and 6.3×10 −3 s −1, respectively. At 30°C, k+1 increased to 2.8×10 3 s −1 M −1 while k−1 showed no such change with a value of 1.8×10 −3 s −1. A continuous Na + influx was demonstrated by both the Na +-dependent leakage current and tetrodotoxin-sensitive Na + current, which resulted in the continuous activation of the Na/K pump. It was thus concluded that the Na/K pump activity was well-maintained in the dissociated rat neostriatal neurons with distinct functional properties and that the activity of the pump was tightly connected with Na + influxes. 相似文献
4.
Electrically evoked sodium currents were recorded under whole-cell patch clamp from undifferentiated HCN-1A cells. Peak sodium currents had a half-maximal activation, Vm0.5, of −22.6 ± 1.0 mV with a voltage dependence, Km, of 7.28 ± 0.39 mV −1. Steady-state inactivation indicated the presence of two types of sodium channel. One type inactivated with Vh0.5 = −93.8 ± 1.2 mV and kh = −6.8 ± 0.4 mV −1. The second type of sodium channel inactivated w Vh0.5 = −44.6 ± 1.5 mV and kh = −7.3 ± 0.4 mV −1. The occurrence of each channel type varied from cell to cell and ranged from 0 to 100% of the total sodium current. No variation in the rate of inactivation was seen when the holding potential was adjusted to eliminate the more negative of the two inactivation components. Application of tetrodotoxin (TTX) or saxitoxin (STX) revealed channel types with two different affinities for each toxin. TTX blocked peak sodium conductance with apparent IC50s of 22 nM and 5.3 μM. STX was more potent, with apparent IC50s of 1.6 nM and 1.2 μM. There was no statistical correlation between toxin sensitivity and steady-state inactivation voltage, suggesting that these properties varied independently among sodium channel types. 相似文献
6.
Pure cultures of rat cerebral capillary endothelium have been used to study the A- and L-systems of amino acid transport. Leucine is taken up by a non-concentrative mechanism that can be saturated, and competivively inhibited by phenylalanine. Uptake is rapid, with equilibiration apparent 3–min (al experiments performed at 37 °C). The KM for transport was 83 μM ± 26(mean ±S.E.M.., n = 3 which is in good agreement with recent vi vivo report using unanesthtissed rats. Alanine was transported by a saturable, concentrative mechanism. Dependence on Na + -ions was demonstrated by lack of specific uptake in Na + -ffree buffer and reduced uptake after preincubation in ouabain — Na +, K + -ATPase inhibitor. The KM was 325 μM ±88 (mean ± S.E.M., n = 3). The finding ac an active A-system transporter in vitro suggests that the cells may have lost the polarity they demonstrate in vivo. The relevance of these findings to transport of nutrients nd drugs across the blood-brain barrier is discussed. 相似文献
7.
The DS (diazepam-sensitive) and DR (diazepam-resistant) lines of mice, selected on the basis of their ataxic response to diazepam, also diverge in the physiologic response of their brain γ-aminobutyric acid A (GABA A) receptors to benzodiazepines, as indicated by augmentation of GABA-mediated chloride flux. Cross-sensitivity and -resistance to other sedatives known to interact with the GABA A-receptor have also been demonstrated in DS and DR mice. Based on the finding that these mice also show cross-sensitivity and -resistance to obtundation by halothane, we predicted that their GABA A-receptors would also exhibit a differential response to halothane as assayed by an in vitro 36Cl − influx assay using purified brain microvesicles. Consistent with this prediction, therapeutic concentrations of halothane enhanced 1 μmol/1 GABA-gated flux with significantly greater potency in DS than in DR mice (halothane EC 50 336±64 μmol/1 (S.E.M.) vs. 605±110 μmol/1, respectively, P = 0.03), but there was no difference in maximal flux enhancement between the two lines (DS 4.7±0.4 nmol·mg −1·3 −1, vs. DR 4.7±0.5nmol·mg −1·3s −). Halothane (500 μmol/1) also shifted the entire GABA concentration-flux relationship significantly to the left, decreasing the EC 50 for GABA in both the DS and DR lines. Importantly, the shift in the GABA concentration-flux response in the presence of halothane was more pronounced in the DS mice (GABA EC 50 1.8±0.4 μmol/1vs.14.7±0.9 μmol/1 without halothane) than in the DR mice (GABA EC 50 4.7±0.6 μmol/1vs.14.7±0.9 μmol/1 without halothane). This effect of halothane was highly significant, both when compared to control, and between the selected lines ( P < 0.001). The findings that halothane enhances GABA-gated flux and enhances GABA's channel gating potency support the hypothesis that differential enhancement of agonist-stimulated chloride permeability at GABA A receptors could be a mechanism underlying the differential obtunding potency of halothane in DS and DR mice. However, at high GABA concentrations halothane decreased maximal chloride flux, more in DS than in DR mice ( P < 0.001), which is not consistent with such a mechanism. 相似文献
8.
Effect of β-agkistrodotoxin (β-AgTx), a presynaptic neurotoxin purified from snake venom, on large-conductance calcium-activated potassium channels (BK Ca) was studied in rat hippocampal CA1 pyramidal neurons using inside-out configuration of patch-clamp technique. The results showed that in equimolar K + (150 mM) and 1 μM intracellular Ca 2+ conditions, internal application of β-AgTx inhibited the activity of BK Ca by reducing open probability ( Po) of the channels in a concentration-dependent manner. High concentration (74 nM) of β-AgTx completely eliminated opening of the channels. However, 37 nM β-AgTx (at −40 mV) decreased Po from 0.49±0.07 to 0.03±0.03, switched two open time constants (0.51±0.32 and 8.77±1.63 ms) to be a single time constant of 0.46±0.40 ms. The results indicate that inhibition of BK Ca by β-AgTx may account for the facilitatory phase of the toxin on acetylcholine release from nerve terminals. 相似文献
9.
The ionic mechanism of the effects of micropressure ejections of hydroxylamine (HOA) and sodium nitroprusside (SNP), nitric oxide (NO) generators, on the membrane of identified neurons (R9–R12) of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion-substitution techniques. Micropressure ejection of HOA and SNP onto the neurons caused a marked depolarization in the unclamped neurons. Clamping the same neurons at their resting potential level (−60 mV) and reejecting HOA and SNP with the same dose produced a slow inward current ( Ii(HOA) and Ii(SNP), 3–7 nA in amplitude, 15–60 s in duration) associated with an increase in input membrane conductance. Bath-applied hemoglobin (50 μM), a nitric oxide scavenger, almost completely blocked Ii(HOA) and Ii(SNP), and 3-isobutyl-1-methylxanthine (IBMX, 50 μM) prolonged and enhanced both Ii(HOA) and Ii(SNP). An intracellular injection of cyclic guanosine 3′,5′-monophosphate (cGMP) into the same neurons produced a slow inward current ( Ii(cGMP)) which resembled the responses to HOA and SNP, and this current was enhanced in IBMX. Bath-applied methylene blue (10 μM), an inhibitor of guanylate cyclase, significantly reduced Ii(HOA) and Ii(SNP). The inward currents induced by HOA, SNP and cGMP were sensitive to changes in the external Na + concentration. These results suggest that extracellular NO can induce a slow inward current associated with an increase in Na + conductance, mediated by an increase in intracellular cGMP. 相似文献
10.
This study examines the effects of hypoxia/hypercapnia and hypoxia/hypercapnia with hypotension (hypotensive-hypoxia/hypercapnia) on blood-to-brain transfer constants ( K1) for sodium and mannitol and brain water and electrolyte contents in newborn piglets. Hypoxia/hypercapnia was induced for 60 min with the piglets breathing a gas mixture of 15% carbon dioxide, 10–12% oxygen, and 73–75% nitrogen adjusted to achieve an arterial pH < 7.15, pO 2 < 40, and pCO 2 > 60 mmHg potension for 20 min by rapid phlebotomy to achieve a mean arterial blood pressure < 40 mmHg. Piglets were studied during 1 h of, and 24 h after resuscitation from hypoxia/hypercapnia (arterial pH 6.9 ± 0.18, pO 2 36 ± 6 mmHg, pCO 2 38 ± 8 mmHg, mean ± S.D.) and 10 min, and 24 h after resuscitation from hypotensive-hypoxia/hypercapnia (mean arterial blood pressure 28 ± 10 mmHg, mean ± S.D.). Values for Kt for sodium and mannitol, measured using the integral technique were 15.9 and 5.2 ml·g −1·min −1 × 10 4 respectively, in 2–4-day-old controls, suggesting that the barrier is fully developed in newborn piglets. Values were not different during or after hypoxia/hypercapnia or 24 after hypotensive-hypoxia/hypercapnia. Ten to forty min after hypotensive-hypoxia/hypercapnia, there was a proportional decrease in the K1 for sodium and mannitol of about 40%. These results suggest that the newborn piglet is similar to the adult with respect to impermeabiity of the blood-brain barrier to ions and small molecules and resistance of this barrier to systemic hypoxia/hypercapnia and hypotension. We suggest that acute decreases in K1 for sodium and mannitol after hypotensive-hypoxia/hypercapnia reflect a reduction in capillary surface area. 相似文献
11.
The rate of inactivation of thrombin by antithrombin III was studied in the presence of heparin using molar concentrations of the reactants in the order: antithrombin III > thrombin > heparin. Reaction rates were calculated assuming either pseudo-first-order kinetics or second-order kinetics. Heparin, up to 0.25 μg/ml (2.2 × 10−2 μM), affected the reaction in such a way that for each 0.1 μg added, the second-order constant increased by 17 × 105 M−1 min−1. Increases in the concentration of antithrombin III at a constant concentration of heparin yielded higher pseudo-first-order constants but fractional contribution of heparin to the overall increment remained approximately the same. In contrast, increases in the ratio of enzyme to heparin resulted in decreases in pseudo-first-order constants. Sodium chloride, in the range from 0.08M to 0.22M, accelerated the inactivation reaction so that an increase by 0.1M of NaCl raised the second-order constant by 12.3 × 105 M−1 min−1. Indirect evidence was obtained supporting the view that NaCl exerts its effect by promoting the recycling of non-stoichiometric amounts of heparin. Calcium chloride, in the range from 1.2 mM to 5.0 mM, also accelerated the inactivation reaction by an unknown mechanism which was distinct from that of NaCl. In the presence of CaCl2, kinetics of inactivation appear to have depended on the choice of the substrate (fibrinogen or N-benzoyl-L-Phe-L-Val-L-Arg-p-nitroanilide-HCl) for measuring residual thrombin activity. Possible reasons for this difference are discussed. 相似文献
12.
The stimulation of adenylate cyclase by dopamine and various β-adrenergic agonists has been investigated in homogenates from 3 areas of cat brain: the cerebral cortex, cerebellum and hippocampus. The purpose of the study was to determine whether the β-adrenergic receptors coupled to adenylate cyclase could be classified as either β 1 and β 2 subtypes in the different regions studied. The stimulation of adenylate cyclase by the β-adrenergic agonist, (−)isoproterenol (5 × 10−6M), was completely blocked by the specific β-adrenergic antagonist, (−)alprenolol (10−5 M), but not by the dopaminergic antagonist, fluphenazine (10−5 M), whereas the stimulation of adenylate cyclase by (−)epinephrine (10−4 M) was blocked to varying extents by these two drugs in each of the 3 regions studied. The (−)epinephrine effect was always blocked in the combined presence of (−)alprenolol and fluphenazine. The adenylate cyclase stimulation by (−)epinephrine which is not blocked by (−)alprenolol was due to interaction of (−)epinephrine with a dopaminergic-sensitive adenylate cyclase which has been characterized in cerebral cortex, hippocampus and cerebellum. Regional differences in the affinity of β-adrenergic-sensitive adenylate cyclase for various agonists were investigated in the presence of fluphenazine (10−5 M). In the cerebellum the potency order was (±)protokylol> (±)hydroxybenzylisoproterenol> (±)isoproterenol> (−)epinephrine> (±)salbutamol> (−)norepinephrine, indicating the presence of a β2-adrenergic receptor. In the cerebral cortex the potency order was (−)isoproterenol> (±)protokylol> (±)hydroxybenzylisoproterenol> (−)epinephrine= (−)norepinephrine((±)salbutamol being inactive). A similar pattern was found in the hippocampus indicating the presence of a β1-adrenergic receptor in these two regions. (±)Salbutamol was a partial agonist in the cerebellum and a competitive antagonist in the cerebral cortex. The ratio of the antagonist potencies of (±)practolol and (±)butoxamine preferential β1- and β2-adrenergic antagonists respectively, to block the stimulation of adenylate cyclase was 25 in the cerebellum, compared to 0.5 in the cerebral cortex and 1.6 in the hippocampus. These results confirm the presence of a β2 subtype of receptor coupled to adenylate cyclase in the former and β1 subtypes in the latter two regions. The comparison between the affinities of a series of β-adrenergic agonists and antagonists for the β-adrenergic receptors coupled with an adenylate cyclase in cerebral cortex and cerebellum with their affinities for well characterized β2-adrenergic receptors in lung and β1-adrenergic receptor in heart substantiated this conclusion. 相似文献
13.
Binding of [ 3H]cyclohexyladenosine (CHA) to the cellular fractions and P 2 subfractions of the goldfish brain was studied. The A 1 receptor density was predominantly in synaptosomal membranes. In goldfish brain synaptosomes (P 2), 30 mM K + stimulated glutamate, taurine and GABA release in a Ca 2+-dependent fashion, whereas the aspartate release was Ca 2+-independent. Adenosine, R-phenylisopropyladenosine (R-PIA) and CHA (100 μM) inhibited K +-stimulated glutamate release (31%, 34% and 45%, respectively). All of these effects were reversed by the selective adenosine A 1 receptor antagonist, 8-cyclopentyltheophylline (CPT). In the same synaptosomal preparation, K + (30 mM) stimulated Ca 2+ influx (46.8±6.8%) and this increase was completely abolished by pretreatment with 100 nM ω-conotoxin. Pretreatment with 100 μM R-PIA or 100 μM CHA, reduced the evoked increase of intra-synaptosomal Ca 2+ concentration, respectively by 37.7±4.3% and 39.7±9.0%. A possible correlation between presynaptic A 1 receptor inhibition of glutamate release and inhibition of calcium influx is discussed. 相似文献
14.
Which vasoactive substances that are synthesized in vivo could induce the release of a sufficient amount of prostacyclin (PGI 2) to inhibit platelet aggregation from the vascular wall was investigated in the isolated dog heart perfused by a modified method of Langendorff. Infusion of 5 μM bradykinin or 25 u/ml crude thrombin into the heart for 30 sec resulted in the transient appearance of inhibitory activity of platelet aggregation. The inhibitory activity was stable at alkaline pH but unstable at acidic pH and thermolabile. The appearance of the inhibitory activity was prevented by treatment of the coronary vessel with 30 μM indomethacin or 1 mM tranylcypromine. These results indicated that the inhibitory activity was caused by PGI2. When 25 μM acetylcholine, 25 μM noradrenaline, 25 μM isoproterenol, 10 μM adenosine triphosphate (ATP 5 μM adenosine, 1 μM angiotensin II, 25 μM histamine or 1 μM serotonin was infused for 30 sec, no inhibitory activity of platele aggregation was observed. Bradykinin (5 × 10 −9 5 × 10 −6 M) and purified thrombin (1 × 10 −9 1 × 10 −7 M) induced a dose-dependent release of PGI 2 which was assayed using a radioimmunoassay for 6-keto-prostaglandin F 1 (6-keto-PGF 1). 相似文献
15.
The occurrence of insuling receptors and biological responses to insulin has been investigated in trypsin-dissociated fetal rat brain cells maintained in culture for 8 days. Binding of [ 125]insulin to brain cells in culture was time- and pH-dependent and 85–90% specific. Porcine insulin competed for [ 125]insulin binding in a dose-dependent manner. Unrelated polypeptides, including angiotensin II, glucagon, bovine growth hormone, and bovine prolactin did not compete for [ 125]insulin binding. The half-life of [ 125]insulin dissociation from receptors at 24°C was 15 min and a plot of ln[B/Bo] vs time suggested two dissociation rate constants of2.7 × 10 −4 sec −1 and5.0 × 10 −5 sec −1. Scatchard analysis of the binding data gave a curvelinear plot which may indicate negative cooperativity or the occurrence of both high affinity( Ka = 2 × 10 11M −1) and low affinity( Ka = 4 × 10 10M −1) sites. Of the estimated total of 4.9 × 10 4 binding sites per cell, 28–30% appear to be high affinity sites. Incubation of cultures with insuling caused a time- and dose-dependent stimulation of [3H]thymidine and [3H]uridine incorporation into TCA-precipitable material. Maximum stimulation of thymidine incorporation (2–5-fold) occured 11 h after incubation with 167 nM insulin. The same concentration of insulin caused a 2.2-fold increase in [3H]uridine incorporation in 2 h. These results indicate that cells cultured from rat brain contain specific insulin receptors capable of mediating effects of insulin on macromolecular synthesis in the central nervous system. 相似文献
16.
Increases in concentration of brain NO are proposed to initiate and mediate migraine headache. Triggered by focal depolarisation, spreading depression (SD) represents a suitable mechanism for eliciting widespread release of nitric oxide. The current study examines the effect of sumatriptan, a 5-HT 1B/1D agonist and effective antimigraine therapy, on free radical release (nitric oxide and superoxide) in SD in the simple and complex cortices of the rat and cat. Following initiation of SD, sumatriptan pretreatment (300 μg kg −1 i.v., 15 min prior to SD) modulated all phases of nitric oxide release associated with each SD in both cats and rats. As a result, superoxide levels were observed to significantly (ANOVA, post hoc LSD) increase versus vehicle treated animals (saline 1 ml kg −1 i.v. 15 min prior to SD) during specific phases of each SD depolarisation. Averaged over all SD depolarisations, mean peak SD nitric oxide levels per depolarisation were 0.73±0.23 μM ( n=29) in cats, and 0.42±0.09 μM ( n=34) in rats. Sumatriptan significantly (Students t-test, P<0.05, two tailed hypothesis, P<0.05) modulated this increase in cortical nitric oxide concentrations to 0.32±0.06 μM ( n=25) and 0.22±0.07 μM ( n=37) in cats and rats. Sumatriptan appears to decrease the amplitude of nitric oxide release but enhances extracellular superoxide concentrations in both lissencephalic and gyrencephalic cortices during SD. 相似文献
17.
We utilize the Lyapunov function method to analyze stability of continuous nonlinear neural networks with delays and obtain some new sufficient conditions ensuring the globally asymptotic stability independent of delays. Three main conditions imposed on the weighting matrices are established. (i). The spectral radius ρ( M−1(| W0|+| Wτ|) K)<1. (ii). The row norm M−1(| W0|+| Wτ|) K+ P−1((| W0|+| Wτ|) KM−1) TP∞<2. (iii). μ 2( W0)+ Wτ2,F<( m/ k). These three conditions are independent to each other. The delayed Hopfield network, Bidirectional associative memory network and cellular neural network are special cases of the network model considered in this paper. So we improve some previous works of other researchers. 相似文献
18.
The impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on GABA A receptor function was studied in acutely isolated neurons from the medial septum/nucleus diagonal band (MS/nDB) of adult rats using whole cell, patch-clamp recordings. In ethanol-naive Controls, GABA (0.3–300 μM) induced concentration-dependent increases in Cl − current with a threshold of 0.3–1 μM, a mean maximal current of 7645 ± 2148 pA at 100–300 μM, an EC 50 of 11.3 ± 1.3 μM and a slope of 1.53 ±0.07. GABA-activated currents in neurons from animals receiving two weeks of ethanol liquid diet treatment did not differ significantly on any of these measures. The rate of GABA A receptor desensitization (t 1/2 = 6.49 ± 1.19 s) estimated as the time required for loss of 50% of peak current during sustained application of 10 μM GABA, as well as the residual steady state current remaining following complete desensitization for controls was unchanged by chronic ethanol. The impact of chronic ethanol treatment on the GABA A receptor modulation by lanthanum and zinc which act as positive and negative allosteric modulators, respectively, was also evaluated. Test pulses of 3 μM GABA in control neurons showed maximal potentiation by 141 ± 30% at ~ 1000 μM lanthanum with an EC 50 of 107 ± 34 μM and a slope of ~ 1. Lanthanum potentiation remained the same following chronic ethanol treatment. Initial estimates based on fitted concentration response curves suggested that maximal inhibition of 3 μM GABA responses by zinc at the level of 70.2 ± 8.5% in control cells was significantly increased by chronic ethanol treatment to 95.3 ± 2.5%, although the IC 50 of 60.2 ± 25 μM was not changed. However, this difference was not supported by direct tests of maximal 3–10 mM zinc concentrations. These results suggest that chronic ethanol treatment, sufficient to induce tolerance and physical dependence, probably does not lead to readily detectible changes in GABA A receptor function in MS/nDB neurons. 相似文献
19.
Objectives: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. Materials and Methods: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. Results: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68±1.2 cm 2 s −2) and POAG (6.79±2.1 cm 2 s −2) than in controls (2.40±0.4 cm 2 s −2). Furthermore, the MAP–CBFV gain was higher in NPG (2.44±0.5 arbitrary units [a.u.]) and POAG (1.99±0.2 a.u.) than in controls (1.21±0.1 a.u.). Conclusion: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases. 相似文献
20.
Serotonin (5-HT) plays an integral regulatory role in mood, anxiety, cognition, appetite and aggressive behavior. Many therapeutic and illicit drugs that modulate these functions act at the serotonin transporter (SERT), thus a mouse model with reduced transporter expression was created to further investigate the effects of differential serotonin reuptake. In the present study, in vivo microdialysis was used to determine homeostatic alterations in extracellular 5-HT levels in unanesthetized SERT knockout mice. SERT −/− mice had significantly higher levels of basal dialysate 5-HT than SERT +/+ mice in striatum and frontal cortex. In addition, although gene-specific increases in 5-HT were evident, neuroadaptive alterations in dialysate dopamine levels were not detected in striatum. Zero net flux microdialysis was utilized to further investigate alterations in extracellular 5-HT. Using this method, a gene dose-dependent increase in extraneuronal 5-HT was observed in striatum (2.8 ± 1, 9.4 ± 1 and 18 ± 3 nM) and frontal cortex (1.4 ± 0.4, 3.5 ± 0.9 and 14 ± 1 nM) in SERT +/+, SERT +/− and SERT −/− mice, respectively. Potassium stimulation revealed greater depolarization-induced increases in striatal 5-HT but not dopamine in SERT −/− mice. Furthermore, dialysate 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in striatum in a gene dose-dependent manner, while DOPAC was unchanged in SERT knockout mice. Finally, determination of monoamine oxidase (MAO) activity revealed no significant differences in KM or Vmax of type-A or type-B isozymes indicating that alterations in SERT expression do not cause adaptive changes in the activities of these key catabolic enzymes. Overall, these results demonstrate that constitutive reductions in SERT are associated with increases in 5-HT in the extracellular signaling space in the absence of changes in dopamine neurochemistry. Furthermore, use of zero net flux microdialysis appears warranted in investigations of serotonergic synaptic function where modest changes in extracellular 5-HT are thought to occur in response to altered uptake. 相似文献
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