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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 107 (2000), S. 885-902 
    ISSN: 1435-1463
    Keywords: Keywords: left ventricle ; norepinephrine ; pressure overload ; catecholamine release.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The purpose of this study was to establish the rat left ventricle (LV) tissue slice system for examination of norepinephrine (NE) release from sympathetic nerve terminals. Moreover, initial experiments were performed to use the LV tissue slice system to examine differences in NE uptake and release following cardiac pressure overload induced by abdominal aortic constriction (AC). Kinetic parameters (Vmax, Km) for the specific uptake of [3H]-NE demonstrated high affinity (Km, 1.94 ± 0.83 μM) and moderate capacity uptake (Vmax, 182 ± 6 fmol/mg/weight/min). Following 10 days of pressure overload, the Vmax for [3H]-NE uptake was significantly reduced (by 46%) in LV slices from AC rats compared to sham-operated (SO) controls. In control rat LV slices preloaded with [3H]-NE, electrically evoked [3H]-overflow was calcium- and stimulus pulse number-dependent. The neuronal uptake inhibitor, desipramine (DMI), increased (by 60%) evoked [3H]-overflow from LV slices. The α2-agonist, UK14304, decreased evoked [3H]-overflow from LV slices in a concentration-dependent manner (maximal reduction of 75%). The β2-agonist, salbutamol, increased evoked [3H]-overflow from LV slices in a concentration-dependent manner (maximal increase of 200%). In separate experiments, the LV tissue slice system was used to examine the effect of pressure overload on evoked [3H]-overflow. Following 10 days of pressure overload, evoked [3H]-overflow from LV slices of AC rats was increased (by 50%) compared to SO control. Increases in evoked [3H]-overflow from LV slices of AC rats compared to SO controls remained evident in the presence of DMI. These results demonstrate the relative importance of NE release and uptake using an in vitro LV tissue slice system. Sympathetic nerve terminals innervating rat LV were demonstrated to possess functional presynaptic α2- and β2-adrenergic receptors. Finally, using this LV tissue slice system, reductions in the uptake velocity and increases in evoked NE release were demonstrated in response to acute cardiac pressure overload.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 345 (1992), S. 153-159 
    ISSN: 1432-1912
    Keywords: DuP 753 ; Angiotensin II ; Dopamine ; Striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to determine if the nonpeptide angiotensin II-1 receptor antagonist DuP 753 after, acute or chronic administration in vivo or after in vitro exposure, altered indices of dopaminergic function in rat striatum. In vivo studies examined the effect of acute and chronic 21-day administration of DuP 753 (10 mg/kg, s.c.) on levels of dopamine (DA) and its metabolite, dihydroxyphenylacetic acid (DOPAC). To determine if chronic treatment with DuP 753 was able to inhibit the pressor response to angiotensin II, a single i.v. dose of angiotensin II (0.1 μg/kg) was administered 18 hours after the last dose of DuP 753. Acute DuP 753 resulted in significantly decreased (14%) levels of DA. Chronic DuP 753 resulted in increased (1.64 fold) levels of DOPAC, although DA levels were not altered. The single i.v. administration of angiotensin II resulted in increased (88%) DOPAC levels regardless of chronic DuP 753. The in vitro effect of DuP 753 (0.1 nM–1.0 μM) on basal and field stimulation-evoked release of DA and DOPAC was determined in superfused striatal slices from drug naive rats. DA was not detected in these experiments. DuP 753 did not alter basal outflow of DOPAC. At low concentrations (1.0–10 nM), DuP 753 decreased (53%) stimulation-evoked DOPAC overflow; however, at concentrations greater than 10 nM, the inhibitory effect was diminished. Nomifensine (10 μM; a DA uptake inhibitor) was included in the superfusion buffer in order to measure the effect of DuP 753 on the concentration of DA in superfusate. DuP 753 had no effect on basal DA and DOPAC outflow. Nomifensine markedly potentiated the DuP 753-induced decrease in stimulation-evoked DOPAC and DA overflow. Pargyline (10 μM; a monoamine oxidase (MAO) inhibitor) was included with nomifensine in the superfusion buffer to examine the contribution of MAO to the DuP 753-induced decrease in dopaminergic neurotransmission. The effect of DuP 753 on DA overflow was not altered by the presence of pargyline. Additionally, angiotensin II (1 and 10 μM) increased the overflow of DOPAC from striatal slices under control conditions. Therefore, the results in vitro suggest that acutely the agonist increases DA neurotransmission and the antagonist decreases DA neurotransmission. In contrast, chronic in vivo adminitration of DuP 753 resulted in increased striatal DOPAC levels indicative of an increased dopaminergic neurotransmission. Therefore, chronic in vivo administration of DuP 753 appears to result in a compensatory response of the dopaminergic system in striatum.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Angiotensin II ; losartan ; norepinephrine ; interscapular brown adipose tissue ; release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine if acute or chronic (21 days) losartan (10mg/kg, s.c.) regulates the renin-angiotensin system in interscapular brown adipose tissue, angiotensin II (AII) content and [3H]overflow from slices preloaded with [3H]norepinephrine were examined. Acute or chronic losartan administration had no effect on AII content. AII increased evoked [3H]overflow from slices from control rats. Losartan administration did not alter basal [3H]outflow or evoked [3H]overflow. Acute losartan administration inhibited AII-induced enhancement of evoked [3H]overflow. Tolerance developed to the inhibitory effect of losartan following chronic administration.
    Type of Medium: Electronic Resource
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