Isosorbide dinitrate and glyceryl trinitrate: Demonstration of cross tolerance in the capacitance vessels

Abstract

Cross tolerance to the arterial effects of sublingual glyceryl trinitrate (GTN) has been demonstrated in subjects taking oral isosorbide dinitrate (ISDN). To determine if cross tolerance also develops in the venous system, the effects of 0.6 mg of GTN on venous capacitance were assessed before (stage A) and during (stage B) therapy with ISDN. Venous capacitance was assessed using the radionuclide blood pool method, with relative changes in regional blood volume measured in the forearm in 6 patients and the splanchnic circulation in 4 patients. Heart rate, blood pressure and blood volume were measured before and at 1-minute intervals for 10 minutes after GTN; there was less than 2% variability in regional blood volume during 6 control measurements. During stage A, 5 minutes after GTN, systolic blood pressure (mean ± standard deviation) decreased by 14% (from 125 ± 15 to 107 ± 19 mm Hg, p < 0.01) and heart rate increased by 17% (from 68 ± 14 to 80 ± 17 beats/min, p < 0.001), while regional blood volume increased to 101 ± 2% at 1 minute (difference not significant [NS]), 111 ± 2% at 5 minutes (p < 0.001) and 107 ± 3% at 10 minutes (p < 0.01) relative to baseline measurements. During stage B, 5 minutes after GTN, systolic blood pressure decreased by only 7% (from 120 ± 10 to 112 ± 10 mm Hg, p < 0.05) and heart rate increased by 7% (from 70 ± 12 to 75 ± 12 beats/min, p < 0.05), while regional blood volume was 100 ± 1 % at 1 minute (NS), 103 ± 1 % at 5 minutes (p < 0.05) and 101 ± 1 % at 10 minutes (NS) after GTN. The changes in blood pressure, heart rate and regional blood volume after GTN during stage B were all significantly less than those observed during stage A. Thus, partial but significant cross tolerance between ISDN and GTN develops in both the arterial and venous systems.