Nitroglycerin and Nitrate Tolerance

Background. The present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance. Methods and Results. Platelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after intracoronary injection of 200 ptg nitroglycerin were measured in 15 patients who had previously received nitrates (nitrates group) and in 16 who had not received any nitrates (no-nitrates group). Platelet cGMP levels increased significantly after nitroglycerin injection in the two groups, but plasma cGMP levels and plasma atrial natriuretic peptide levels did not change. The percent increase in platelet cGMP levels and the percent dilatation of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries after nitroglycerin injection were higher in the no-nitrates group than in the nitrates group (platelet cGMP levels: artery, 74.2±18.3% versus 11.5±4.2%, P<.01; vein, 73.6+22.9%o versus 9.0±3.1%, P<.01; coronary dilatation: LAD, 46.7±6.0%o versus 9.9±2.5%, P<.01, LCx, 51.2+8.7% versus 6.1±3.0%o, P<.01). The percent increase in platelet cGMP levels was significantly correlated with the percent dilatation of the coronary arteries (LAD: r=.90, P<.01; LCx: r=.92, P<.01) in the no-nitrates group and not in the nitrates group. Conclusions. These results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin. (Circulation 1993;88:29-36)