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  • 1
    Digitale Medien
    Digitale Medien
    The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs (1991)
    Springer
    Acta neurochirurgica 110 (1991), S. 185-188 
    Details
    ISSN: 0942-0940
    Schlagwort(e): HA1077 ; cerebral vasospasm ; subarachnoid haemorrhage ; cerebral blood flow ; calcium antagonist
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p〈0.05) and Hood velocity (48% of control, p〈0.05), with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1–0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01400689
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  • 2
    Digitale Medien
    Digitale Medien
    Pronounced direct inhibitory action mediated by adenosine A1 receptor and pertussis toxin-sensitive G protein on the ferret ventricular contraction (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 282-289 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Adenosine ; Phenylisopropyladenosine ; Adenosine receptors ; Negative inotropic effect ; G proteins ; Ferret ventricular myocardium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary An adenosine A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA) elicited a pronounced negative inotropic effect with the EC50 value of 0.69 μmol/1 in the presence of a β-adrenoceptor blocking agent bupranolol (0.3 μmol/1) in the isolated ferret papillary muscle. The negative inotropic effect of R-PIA was not associated with changes in cyclic AMP level. Adenosine and other A1 receptor agonists also elicited a negative inotropic effect. DPCPX (1,3-dipropyl-8-cyclopentyl xanthine) antagonized the negative inotropic effect of R-PIA in a competitive manner (pA2 value = 8.4). The inhibitory action of R-PIA was markedly attenuated in the ventricular muscle preparation isolated from ferrets pretreated with pertussis toxin that caused ADP-ribosylation of 39 kDa proteins in the membrane fraction. In the membrane fraction derived from the ferret ventricle, [3H]-DPCPX bound to a single binding site in a saturable and reversible manner with high affinity (Kd value = 1.21±0.41 nmol/l; B max = 12.8±3.02 fmol/mg protein; n = 7). The binding characteristics of [3H]-DPCPX in the rat ventricle (Kd value = 1.51 ±0.09 nmol/l; B max = 12.7±1.47 fmol/mg protein; n = 5) were similar to those in the ferret. On the other hand, the content of Go, a major pertussis toxin-sensitive G protein in the ferret heart, was much higher in the ferret than in the rat ventricle. The present results indicate that adenosine receptors may play an important role in the inhibitory regulation of ventricular contractility in the ferret in contrast to other mammalian species. The signal transduction process subsequent to agonist binding to A1 receptors including the pertussis toxin-sensitive G protein and ion channels may be responsible for the unique inhibitory action of adenosine in this species.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00169157
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