Stimulation of coronary vascular prostacyclin and inhibition of human platelet thromboxane A 2 after low-dose nitroglycerin

Abstract

Although glyceryl trinitrate (GTN) is an efficient agent in the treatment of angina pectoris, the underlying mechanism of action is poorly understood. We report here, that GTN at nanomolar concentrations stimulates the PGI 2-formation of coronary vessels and by this mechanism inhibits thromboxane biosynthesis of human platelets. Bovine coronary arteries were incubated in Krebs-Henseleit buffer and exhibited a time-dependent PGI 2-release, amounting to 25 ± 4 pmoles/100 mm 2 surface within 20 min. In presence of GTN (1.3 and 13 nM) this basal release of PGI 2 was significantly enhanced to 42 ± 7 and 51 ± 8 pmoles/100 mm 2, respectively (n = 12, P < 0.05). GTN alone did not modify the release of “rabbit aortic contracting substance” (RCS) following stimulation of washed human platelet suspensions (WPS) by 0.6 IE/ml thrombin. However, addition of aliquots of the vessel incubates to the WPS prior to thrombin inhibited the RCS-formation by 27 ± 4% (n = 10, P < 0.05) and this reaction was significantly enhanced to 60 ± 4%, when incubates of GTN-treated vessels were used (n = 10, P < 0.05). Similar data were obtained with rabbit arterial tissue. This inhibition of RCS-release was prevented, when previously heated vessels were used and was mimicked by exogenous PGI 2 (8.1 nM). We conclude, [1] that GTN by stimulation of vascular PGI 2 inhibits the platelets' TXA 2-formation and [2] that this effect might be involved in the beneficial actions of this agent in acute myocardial ischemia.