Receptor-mediated changes in vessel tone of fresh and aged bovine cerebral arteries in vitro.
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Biomedical subjects
Publications and source records attributed to R Verheggen.
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This study was designed to investigate the effects of Naftidrofuryl on platelet function and vessel tone and additionally platelet vessel wall interactions. It is shown that Naftidrofuryl displays a spasmolytic activity against a variety of different vasoconstrictors, including 5-HT, PGF2 alpha, U 46.619 and KC1 and inhibits platelet secretion. These effects are observed at concentrations of the compound equal to or higher than 1 mumol/l and might contribute to the clinical efficacy of the drug.
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The role of platelet-derived vasoconstrictors in coronary vasospasm was studied using arachidonic acid-stimulated washed human platelets (WPS). Transfer of this system into an organ bath, containing bovine coronary arteries (BCA) and a mixture of blocking agents resulted in a biphasic contraction, consisting of a first phase, mediated by release of thromboxane (TX) A2 and a second phase, mediated by release of 5-hydroxytryptamine (5-HT) from the WPS (1,2). Treatment of the WPS with 4-[2-(benzenesulfonamido)-ethyl]-phenoxyacetic acid (BM 13.177) (0.03-3 mumol/L) prior to stimulation revealed a concentration-dependent inhibition of the 5-HT component of the contractile response with a minor reduction of the TXA2 component of contraction and enhanced amounts of immunoreactive TXB2 in the bath fluid. Treatment of the BCA with BM 13.177 prior to addition of stimulated WPS resulted in a significant reduction of the TXA2 component of contraction, by 56% at 30 mumol/L whereas 3 mumol/L were ineffective. The 5-HT component of contraction was enhanced. For comparison, the IC50 for BM 13.177 to inhibit PGF2 alpha-induced contractions was 6 mumol/L and that to inhibit U-46,619 was 0.5 mumol/L. BM 13.177 was at least 1 order of magnitude more potent as an inhibitor of U-46,619 than of PGF2 alpha- or TXA2-induced contractions. It is concluded that BM 13.177 is a weak inhibitor of TXA2-mediated contractions of coronary vessels, suggesting different thromboxane receptors in coronary vessels and platelets.
The actions of prostacyclin and its synthetic analog iloprost on the release and action of platelet-derived serotonin (5-HT) and thromboxane (TX) A2 were studied in vitro. Washed human platelet suspensions (WPS) (4 X 10(8) platelets/ml) were stimulated with arachidonic acid (AA) (30 mumol/L) and the incubate transferred into an organ bath containing bovine coronary arteries (BCA) in Krebs-Henseleit buffer supplemented with a mixture of blocking agents, including indomethacin. This resulted in a biphasic contraction of the coronary arteries, consisting of first, a TXA2-mediated response and second, a 5-HT-mediated response. The 5-HT-mediated reaction was dose-dependently inhibited by methysergide (IC50: 80 nmol/L). Treatment of the WPS with prostacyclin (PGI2) or iloprost prior to stimulation by AA resulted in a dose-dependent inhibition of the 5-HT-mediated contraction, due to inhibition of 5-HT release. The TXA2-mediated component, as well as the concentration of immunoreactive TXB2 in the bath medium, remained unchanged. Addition of PGI2 or iloprost to the BCA prior to transfer of stimulated WPS to the bath medium was followed by a dose-dependent inhibition of both phases. This, however, required concentrations of 100 nmol/L 5-HT and greater than 300 nmol/L TXA2 (IC50), which already produced a nearly complete direct relaxation of the vessel preparations (EC50: 30 nmol/L). It is concluded that a significant spasmolytic action of prostacyclins against platelet-derived vasoconstrictors in vivo might only be obtained at concentrations that already produce considerable direct effects on vessel tone.
Neurocysticercosis is no medical rarity but in non-endemic countries especially, a high degree of physician awareness is necessary for diagnosis. The case of a German female patient who had focal seizures for the first time at the age of 23 caused by a cerebral cyst of cysticercus cellulosae is presented. Only surgical removal and subsequent histological examination allowed diagnosis while diagnostic investigation yielded no pathological findings.