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  • 1
    ISSN: 1432-1912
    Keywords: Postsynaptic α 1- α 2-adrenoceptors ; Methoxamine ; B-HT 920 ; Calcium antagonists ; Divalent metal ions ; Calcium ions ; Vasoconstriction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of various calcium antagonists and divalent metal cations on the pressor responses induced by the selective α 1-adrenoceptor agonist methoxamine and the selective α 2-adrenoceptor stimulating agent B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine) was studied in pithed rats. 1. The calcium antagonists verapamil, D 600 and nifedipine, when given intraarterially (i.a.) in doses up to 1 mg/kg did not influence the pressor effects of methoxamine. Only higher amounts of these calcium antagonistic drugs (1–3 mg/kg i.a.) somewhat reduced this pressor response. 2. The vasoconstriction due to B-HT 920, as reflected by the increase in diastolic pressure, was markedly inhibited by verapamil, D 600 and nifedipine in a dose-dependent manner. In low doses a parallel displacement to the right was observed, whereas in higher amounts the shift was non-parallel. 3. The divalent cations Mn2+, Ni2+ and Co2+ (0.05–0.15 mmol/kg i.a.) hardly affected the pressor effect of methoxamine, whereas B-HT 920-induced vasoconstriction was highly sensitive to these metal ions. La3+ and Mg2+ were ineffective. 4. The calcium antagonists verapamil, D 600 and nifedipine displayed only minor affinities for [3H]prazosin (α 1) as well as [3H]clonidine (α 2) binding sites of rat brain membranes. 5. It is concluded that an influx of extracellular Ca2+ is necessary for the vasoconstriction in vivo initiated by stimulation of vascular postsynaptic α 2-adrenoceptors. On the other hand, vasopressor responses to α 1-adrenoceptor stimulation are not directly dependent on a transmembrane influx of calcium ions.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: B-HT 920 ; B-HT 958 ; Postjunctional vascular α2-adrenoceptors ; Partial and full agonism ; Calcium entry blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following i.v. bolus injections into pithed normotensive rats, the maximal diastolic pressor responses to B-HT 920 and B-HT 958 amounted to 115 and 35 mm Hg, respectively. Prazosin (0.1 mg/kg, i.v.,-15 min) was without effect on the log dose-pressor effect curve of B-HT 958, whereas yohimbine (1 mg/kg, i.v.,-15 min) shifted this curve about 30-fold to the right, showing the exclusive participation of α2-adrenoceptors in the vasoconstrictor response to B-HT 958. In doses of 10 and 30 mg/kg, B-HT 958 displaced the log dose-vasoconstrictor effect curve of B-HT 920 approximately 6- and 30-fold, respectively, to the right, illustrating the partial agonism of B-HT 958 at postjunctional vascular α2-adrenoceptors. Despite the marked difference in intrinsic activity of B-HT 920 and B-HT 958, the calcium entry blocker nifedipine exhibited a comparable inhibitory action on the vasopressor responses to both agonists. This finding indicates that partial and full agonism at vascular α2-adrenoceptors are not related to the susceptibility of the initiated pressor response to inhibition by calcium entry blockade.
    Type of Medium: Electronic Resource
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