Mechanisms of nitrate tolerance a review英文电子书.pdf

Cardiovascular Drugs and Therapy 4: 247-252, 1990 ~r Kluwer AcademicPublishers, Boston. Printed in U.S.A. Mechanisms of Nitrate Tolerance: A Review Richard J. Katz Division of Cardiology, George Washington University Medical Center, Washington, DC, USA Summary. With the increased use of long-acting nitroglyc- stantiated these clinical observations [3]. The develop- erin preparations, there has been greater recognition of the ment of tolerance and cross tolerance to organic ni- problem of nitrate tolerance. In recent )ears extensive re- trates has been reproduced with nitroglycerin and search has broadened our understanding of the mechanisms of nitroglycerin action and the mechanisms of drug attenua- isosorbide dinitrate [19]. tion. This paper reviews the current state of knowledge re- The greater recognition of the problem of nitrate garding nitroglycerin tolerance, with an emphasis on the tolerance has intensified investigations into the mech- concepts of cellular and neurohumoral mechanisms of drug anisms of drug attenuation. This review summarizes attenuation. The discussion includes potential approaches to the current concepts of nitrate tolerance and the impli- prevent nitrate tolerance, including the introduction of a ni- trate-free interTal, or concomitant administration of sulfhy- cations for therapeutic strategies to avoid or minimize dryl donors or neurohumoral blocking agents. this pharmac