Possible mechanisms of nitrate tolerance.
Prolonged exposure to organic nitrates has been shown to lead to the rapid development of tolerance to the peripheral and coronary vasodilatory effects of these drugs. As a result of this phenomenon, the hemodynamic and anti-ischemic effects of nitrates may be rapidly attenuated in patients with ischemic heart disease, congestive heart failure, or both. This nitrate tolerance appears to be both dose- and time-dependent. Likely mechanisms proposed for its development are multifactorial and include depletion of sulfhydryl groups, a nitrate-mediated increase in blood volume, and neurohormonal stimulation with activation of vasoconstrictive mechanisms.
Elkayam
U
U
Department of Medicine, University of Southern California (USC) Los Angeles 90033.
Mehra
A
A
Shotan
A
A
Osprzega
E
E
D003326:Coronary Circulation / Q000187:drug effects; D004361:Drug Tolerance; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009566:Nitrates / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D009566:Nitrates