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 effec ts and its hypotensive action. In addition, beta-adrenolytic drugs are known to inhibit platelet aggregation in vitro possibly through lower ing of calcium ions level. Here, we report that in rats sotalol at a d ose of 10-20 mg/kg i.v., apart from hypotension, evokes instantaneous thrombolytic effect. This is associated with an increase in plasma lev el of tissue plasminogen activator (t-PA). In vitro, sotalol at a conc entration of 1-100 mu M inhibits thrombogenesis on surface of rabbit a orta endothelium superfused with blood. Sotalol also has a weak anti-a ggregatory activity (IC50 similar to 500-1000 mu M) in human platelet rich plasma (PRP). Since the thrombolytic and fibrinolytic but not hyp otensive 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, N-G-nitro-L-argini ne (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 o f sotalol, may play different roles: prostacyclin may be responsible f or fibrinolytic, thrombolytic and antithrombotic properties, while nit ric oxide may take part in the mechanism of sotalol-induced hypotensio n.