Inhibition of Nitrate Tolerance without Reducing Vascular Response during Eccentric Dosing of Nitrates

It has been reported that the nitrate tolerance related to continuous dosing of nitrates reduces drug efficacy, and therefore eccentric dosing of nitrates is recommended. In this study, we investigated the appearance of nitrate tolerance related to continuous dosing of nitrates and prevention of nitrate tolerance during eccentric dosing by comparing the grade of coronary dilatation after sublingual nitroglycerin. Of 26 patients with ischemic heart disease who underwent elective cardiac catheterization, 8 patients were continuously administered nitrates, 8 patients were eccentrically administered nitrates, and 10 patients were not treated. We compared the coronary response to sublingual nitroglycerin among the 3 groups. In a coronary vessel without significant stenosis, the coronary vessel area, coronary lumen area, and mean coronary blood flow velocity after sublingual nitroglycerin were measured using intravascular ultrasound (IVUS). In the continuous dosing group, the maximal rate of change in the vessel area after sublingual nitroglycerin was 105 +/- 1 (mean +/- SEM) %, significantly lower than those in the untreated group and the eccentric dosing group (114 +/- 2%, 114 +/- 2%) (p < 0.01, respectively). In conclusion, eccentric dosing of nitrates inhibited the appearance of nitrate tolerance without reducing vascular response.