Nitroglycerin Uptake and Cyclic Guanosine Monophosphate Production in Peripheral Vascular Bed after Intravenous Administration of Nitroglycerin.

The purpose of this study was to determine the relationships between the hemodynamic e ffects, plasma nitroglycerin (NTG) levels, and plasma cGMP levels with short-and longterm administration of NTG.In the first part of the study, 20 patients with old myocardial infarction received increasing stepwise dosages of intravenous NTG ffom 0.05 to 05μg/kg/min. Coronary diameters were measured using coronary angiography and measurements were made on hemodynamic parameters as well as arterial and venous plasma NTG and cGMP levels.In the second part of the study, 15 patients with congestive heart failure or unstable angina received intravenous NTG infusions at a constant rate for 24 hours. Hemodynamic parameters as well as arterial and venous plasma NTG and cGMP levels were measured repeatedly over this 24-hour period.In the first part of the study, there was a significant arterialvenous plasma NTG concentration gradient and cGMP production (venousarterial plasma cGMP concentration gradient) was observed at the peripheral vascular bed during short-term NTG administration. Pulmonary arterial wedge pressure and mean aortic pressure dose-dependently decreased, and the epicardial coronary artery was dose-dependently dilated. Arterial plasma NTG levels were significantly correlated with percentage changes in hemodynamic parameters over short-term administration and this relationship was found to be independent of the venous plasma levels of NTG. Based on the above hemodynamic effects and the plasma concentration of NTG, the arterial plasma NTG level can be said to be a better index of NTG effects than the venous level.In the second part of the study the systemic blood pressure and pulmonary arterial wedge pressure fell and remained significantly lower than the baseline values throughout the initial 6 hours, but did not differ significantly from the baseline at either 12 or 24 hours. The arterial-venous NTG concentration gradient was diminished at the 24-hour point to a level which differed significantly from the values at the 1-hour point. The production of cGMP also dminished.These findings suggest that extensive uptake and/or metabolism of NTG by the peripheral vascular bed may occur in the non-tolerant state but not in the nitrate tolerant state.