Thrombolytic activity of beta-adrenolytic drug, sotalol.
Sotalol is a beta-adrenoreceptor blocking drug, the clinical efficacy of which has been linked up to its negative chrono- and inotropic effects and its hypotensive action. In addition, beta-adrenolytic drugs are known to inhibit platelet aggregation in vitro possibly through lowering of calcium ions level. Here, we report that in rats sotalol at a dose of 10-20 mg/kg i.v., apart from hypotension, evokes instantaneous thrombolytic effect. This is associated with an increase in plasma level of tissue plasminogen activator (t-PA). In vitro, sotalol at a concentration of 1-100 microM inhibits thrombogenesis on surface of rabbit aorta endothelium superfused with blood. Sotalol also has a weak anti-aggregatory activity (IC50 approximately 500-1000 microM) in human platelet rich plasma (PRP). Since the thrombolytic and fibrinolytic but not hypotensive effects of sotalol were inhibited by cyclooxygenase inhibitor, indomethacin, while its hypotensive but not thrombolytic potency was dimished by an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (L-NNA), we have linked up the sotalol-induced effects in vivo with the release of prostacyclin and nitric oxide. Our data point out to a possibility that prostacyclin and nitric oxide concomitantly released from endothelium and/or from other blood cells after administration of sotalol, may play different roles: prostacyclin may be responsible for fibrinolytic, thrombolytic and antithrombotic properties, while nitric oxide may take part in the mechanism of sotalol-induced hypotension.
Korbut
R
R
Jagiellonian University Medical School, Cracow, Poland.
Swies
J
J
Marcinkiewicz
E
E
Gryglewski
R J
RJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013015:Sotalol / Q000494:pharmacology*; D013927:Thrombosis / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D013015:Sotalol; D010959:Tissue Plasminogen Activator