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  • 1
    ISSN: 1432-1912
    Keywords: N-ethylmaleimide ; Muscarinic receptor ; Inotropy ; Chronotropy ; Rat right atrium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-ethylmaleimide (NEM) rapidly blocked the negative chronotropic effect of carbachol on rat right atrium. In contrast, NEM did not reduce the negative inotropic response to muscarinic (M) receptor stimulation. Carbachol inhibited the specific binding of [3H]-N-methylscopolamine ([3H]-NMS) to membranes of rat atria as reflected by a shallow inhibition curve. Both guanosine triphosphate (GTP) and NEM shifted the [3H]-NMS inhibition curves of carbachol to the right. Pretreatment of the atrial membranes with NEM abolished the GTP-induced rightward shift. However, when instead of the membranes the intact atria were pre-incubated with NEM, no interaction between NEM and GTP in the membranal preparation was observed. The results indicate that NEM sharply discriminated between the inotropic and chronotropic effects to M-receptor stimulation in rat atria. The inhibitory effect of NEM on the M-receptor-mediated negative chronotropic effect in rat atrium cannot be explained by an interaction of the sulfhydryl reagent with GTP-binding proteins, like Ni or No.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1619-7089
    Keywords: Iodine-123 metaiodobenzylguanidine ; Rats ; Diabetes mellitus ; Hypertension ; β-Adrenoceptor density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 μCi [123I]MIBG. Initial myocardial uptake and washout rates of [123I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular β-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of β-adrenoceptors, indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [123I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in β-adrenoceptor density were found, whereas [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or ß-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [123I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.
    Type of Medium: Electronic Resource
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