Systemic effects of S-nitroso-glutathione in the human following intravenous infusion.
Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet aggregation. At present the clinical use of NO donors as inhibitors of platelet activation is limited by their concomitant hypotensive effect. The new NO donor S-nitroso-glutathione (GSNO) has a significant antiplatelet effect at doses that cause only a small decrease in blood pressure in rats. We have examined the antiplatelet and vasodilator properties of this nitrosothiol following systemic intravenous infusion in the 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 in a platelet-ionized calcium lumiaggregometer on blood samples taken both before and after the infusions. Side effects such as headache or palpitations occurred only in two subjects at the highest infusion rate of 250 micrograms min-1. Blood pressure and pulse did not vary significantly 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 vasodilator and therefore potentially represents a more clinically useful NO donor than has so far been available where an anti-thrombotic effect is required.
Chelsea and Westminster Hospital, London, UK.
B
B
Ramsay
M
M
Radomski
A
A
De Belder
J F
JF
Martin
P
P
Lopez-Jaramillo
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D026422:S-Nitrosoglutathione; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D026422:S-Nitrosoglutathione; D005978:Glutathione