Mechanism of Nitrate Tolerance and Prevention Strategies

Primary Mechanisms

• Nitrates require enzymatic biotransformation by mitochondrial aldehyde dehydrogenase to produce vasoactive nitric oxide, a process that depends on sulfhydryl cofactors, according to the American College of Cardiology, 1, 2

Prevention Strategies

• The American College of Cardiology/American Heart Association guidelines recommend a nitrate-free interval of at least 10 hours to minimize tolerance development, with a strength of evidence level of high, 3, 4, 5, 6, 7, 8
• Combining nitrates with ACE inhibitors or hydralazine may help prevent tolerance development, as suggested by the American Heart Association, with moderate strength of evidence, 3, 4, 5, 6, 7, 8