To evaluate whether there is cross-tolerance to the circulatory effects of isosorbide dinitrate and nitroglycerin, six subjects were given 120 mg/day of sustained-action isosorbide dinitrate in three divided doses for six to eight weeks. Prior to and during the last week of long-term isosorbide dinitrate administration, the effects of sublingually given nitroglycerin (0.9 mg) on plethysmographically measured calf blood flow and venous volume at 30 mm Hg (VV) were measured on three occasions and averaged. Although the arteriolar dilation produced by nitroglycerin was unaltered by isosorbide dinitrate, the venodilation was significantly attenuated. The VV increased from 3.00 to 3.28 ml/100 ml (P <.02) with nitroglycerin prior to isosorbide dinitrate administration, but failed to increase with nitroglycerin during the long-term administration of isosorbide dinitrate (2.95 to 2.95 ml/100 ml, P>.5).
(JAMA 234:166-170, 1975)
Zelis R, Mason DT. Isosorbide DinitrateEffect on the Vasodilator Response to Nitroglycerin. JAMA. 1975;234(2):166–170. doi:10.1001/jama.1975.03260150036016