SYSTEMIC EFFECTS OF S-NITROSO-GLUTATHIONE IN THE HUMAN FOLLOWING INTRAVENOUS-INFUSION

Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet ag gregation. At present the clinical use of NO donors as inhibitors of p latelet activation is limited by their concomitant hypotensive effect. The new NO donor S-nitroso-glutathione (GSNO) has a significant antip latelet effect at doses that cause only a small decrease in blood pres sure in rats. We have examined the antiplatelet and vasodilator proper ties of this nitrosothiol following systemic intravenous infusion in t he human. GSNO was administered intravenously to 10 normal females of reproductive age noting changes in blood pressure, pulse and reported side effects. Ex vivo platelet aggregation to ADP was then performed i n a platelet-ionized calcium lumiaggregometer on blood samples taken b oth before and after the infusions. Side effects such as headache or p alpitations occurred only in two subjects at the highest infusion rate of 250 mu g min(-1). Blood pressure and pulse did not vary significan tly during the study. Ex vivo platelet aggregation in response to ADP was significantly reduced by the infusion. These results suggest that GSNO is a more potent inhibitor of platelet activation than it is a va sodilator and therefore potentially represents a more clinically usefu l NO donor than has so far been available where an anti-thrombotic eff ect is required.