METHYLENE-BLUE INHIBITS THE ANTITHROMBOTIC EFFECT OF NITROGLYCERIN

Objectives. The aim of this study was to examine whether cyclic guanosine monophosphate (GMP) may be involved in the antithrombotic action of nitroglycerin. Background. Nitroglycerin has been shown to inhibit platelet function in vitro by stimulating prostacyclin or inhibiting thromboxane A2 production, or both. Nitroglycerin has also been shown to possess potent antithrombotic properties in vivo. However, the mechanism of this antithrombotic effect is unclear. Methods. Nitroglycerin was infused to produce a 10% decrease in mean arterial pressure in 27 normal pigs by exposing their circulating arterial blood to porcine aortic media in an ex vivo perfusion chamber. Eight pigs received an infusion of nitroglycerin alone; eight received an infusion of methylene blue, a guanylate cyclase inhibitor, followed by nitroglycerin infusion and five pigs received an infusion of nitroglycerin followed by methylene blue and subsequent infusion of cyclic GMP. Results. With nitroglycerin alone, quantitative autologous indium-111-labeled platelet deposition (x10(6)) on the aortic media was decreased to 63.9 +/- 10.4% (p = 0.01) of the baseline control platelet deposition. Methylene blue given before nitroglycerin tended to increase platelet deposition relative to baseline and platelet deposition after nitroglycerin was 142 +/- 35% (p = NS) of baseline value. In pigs that received all three agents, nitroglycerin reduced platelet deposition to 42.3 +/- 12.2% of baseline value, this decrease was then attenuated by subsequent methylene blue infusion but was enhanced by cyclic GMP infusion to 16.4 +/- 3.8% of baseline value (p = 0.006 vs. baseline control and p = 0.02 versus methylene blue infusion). Conclusions. Guanylate cyclase inhibition with methylene blue abolishes the antithrombotic effect of nitroglycerin, which can be enhanced by cyclic GMP.