Dissociation of vascular tolerance and plasma norepinephrine adjustment during long-term nitrate therapy in human coronary arteries

Objective We examined whether changes in plasma norepinephrine (NE) concent ration contribute to the development of nitrate tolerance in human coronary arteries. Methods Patients with stable angina were randomized to receiving nitrate (isosorbide dinitrate: ISDN or nitroglycerin: TNG) infusion for 30 minutes (group A), 48 hours (group B), or 78 hours (group C), Coronary dia meters were measured angiographically at baseline (CT), during maximum dila tion by ISDN (N1), at the end of nitrate infusion (N2) and after additional ISDN (1 mg) injection (N3), Results In groups A and B, N1, N2, and N3 were greater than CT, and there was no significant difference between N1, N2, a nd N3 for each group, In group C, N1 and N3 were greater than CT, but there was no difference between CT and N2, in the development of nitrate toleran ce, In group A, NE increased significantly during nitrate infusion (304+/-1 63 vs, 418+/-273 pg/ml), NE did not change in groups B and C, Conclusion Th e change in NE concentration is not a primary contribution to the developme nt of nitrate tolerance.