Prevention of nitroglycerin tolerance with diuretics

Tolerance to prolonged nitroglycerin (NTG) may be due to drug-induced intravascular expansion. To test the hypothesis that concomitant diuretics may reduce volume expansions and thus prevent NTG tolerance, we studied 23 healthy volunteers randomized to hydrochlorthiazide or placebo before and during 74-hour continuous NTG exposure. Venodilator response to NTG was tested serially with venous forearm plethysmography. In the preNTG patch phase venodilator response was similar in both the placebo and diuretic groups. Venodilator capacity was compared after "acute" (2-hour) and "chronic" (74-hour) NTG exposure with NTG patches. Attenuation to NTG was seen in the placebo group, but NTG venodilator activity was fully maintained in the diuretic group. These data suggest that diuretics may be helpful in the prevention of NTG tolerance.