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

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 less than 0.01) and heart rate increased by 17% (from 68 +/- 14 to 80 +/- 17 beats/min, p less than 0.001), while regional blood volume increased to 101 +/- 2% at 1 minute (difference not significant [NS]), 111 +/- 2% at 5 minutes (p less than 0.001) and 107 +/- 3% at 10 minutes (p less than 0.01) relative to baseline measurements.(ABSTRACT TRUNCATED AT 250 WORDS)