COMPARISON OF HEMODYNAMIC-EFFECTS AND PLASMA CYCLIC GUANOSINE-MONOPHOSPHATE OF NICORANDIL AND NITROGLYCERIN IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Hemodynamic tolerance has been observed within several hours of continuous infusion of nitroglycerin (NTG). We examined the hemodynamic parameters as well as femoral arterial and venous cyclic guanosine monophosphate (cGMP) concentrations during intravenous infusion of NTG or nicorandil, a nitrate and potassium channel opener, in patients with congestive heart failure. Doses of NTG or nicorandil were titrated to achieve a greater than or equal to 25% reduction in pulmonary capillary wedge pressure (PCWP) within 1 hour, and the infusion was maintained at a constant rate for 24 hours. The reduction in PCWP and mean arterial blood pressure was identical after a 1-hour infusion of either NTG or nicorandil. In the NTG group, PCWP and mean blood pressure were not significantly different from the baseline value at 12 hours, but in the nicorandil group PCWP and mean blood pressure remained significantly lower than the preinfusion value for 24 hours. The cGMP production with NTG (assessed by the difference between the plasma arterial and venous cGMP level) paralleled the changes in PCWP, suggesting that the plasma arteriovenous cGMP difference is a biochemical indicator of nitrate tolerance. Although the sustained decrease in PCWP was observed in the nicorandil group, cGMP production with nicorandil was also attenuated at 24 hours of continuous infusion. These findings suggest that the absence of the hemodynamic tolerance af nicorandil, a nitrate and potassium channel opener, is likely due to its action os a potassium channel opener, and not to its nitrate activity.