This study assessed the inhibitory effect of nitroglycerin and sodium nitroprusside on platelet aggregation in a model of platelet activation across coronary circulation. Platelet aggregation is believed to contribute to the precipitation of acute ischemic syndromes. We previously showed that rapid atrial pacing in patients with stable coronary artery disease (CAD) causes platelet hyperaggregability during blood passage in coronary circulation. Because nitroglycerin and sodium nitroprusside have been shown to inhibit platelet aggregation, we examined the effect of these drugs on this model of platelet activation. During catheterization of 19 patients with CAD (> 50% diameter narrowing of epicardial coronary arteries), we measured platelet aggregation (using whole blood platelet aggregometry) on blood samples obtained simultaneously from the coronary sinus and aorta at rest, and 2 minutes after onset of rapid atrial pacing. This procedure was repeated during an intravenous infusion of either nitroglycerin (n = 9) or sodium nitroprusside (n = 10). There was no arteriovenous difference in platelet aggregation under resting conditions. Atrial pacing caused an increase in platelet aggregation in coronary sinus blood (+64 +/- 9%; p < 0.01), but not in arterial blood (15 +/- 12% decrease; p = NS). This increase was transient and returned toward baseline 10 minutes after termination of pacing. Although resting platelet aggregation was not affected by nitroglycerin or sodium nitroprusside, activation of platelets with atrial pacing across the coronary bed was stopped by pretreatment with therapeutic doses of nitroglycerin or sodium nitroprusside. When coronary blood flow increases in patients with CAD, platelets are activated and aggregate more easily. This activation can be blunted by pretreatment with nitroglycerin or sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)