Long- term nitroglycerin therapy is associated with endothelial dysfunction via accumulation of the same oxygen free radi- cals that seem to be beneficial in short-term administra- tion.870,871 The oxygen free radical accumulation increases arterial sensitivity to vasoconstrictors such as angiotensin II, which can be counteracted by concomitant treatment with an ACE inhibitor or hydralazine.872 875 Importantly, these phys- iological changes are independent of dose or the presence or absence of a nitrate-free interval and can result in a decrease in the anginal threshold during the nitrate-free interval.876 Further research to better understand the balance between the long-term benefits and safety concerns of these compounds is warranted in patients with SIHD. Despite these physiological observations, nitrates improve exercise tolerance, time to ST-segment depression, and time to onset of angina in patients with SIHD, albeit in small patient studies conducted for relatively short periods.876 878 Comparisons of nitrates to beta blockers or calcium channel blockers have not shown significant differences with regard to weekly anginal episodes, time to ST-segment depression, total exercise time, or sublingual nitroglycerin use.420 With- drawal for adverse effects was also not statistically different between the drug classes. All patients with SIHD should be prescribed sublingual nitroglycerin tablets or nitroglycerin spray for immediate relief of angina. Most patients respond within 5 minutes of taking 1 to 2 sublingual dose(s) of 0.3 to 0.6 mg. Nitroglyc- erin spray is available in a 0.4-mg metered-dose canister that dispenses 200 doses. The tablets should be placed under the tongue and not swallowed. If the spray is used, it should be applied to the tongue and not swallowed or inhaled. If additional doses are necessary, they should be taken at 5-minute intervals, for a maximum dose of #1.2 mg within 15 minutes. 