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Intermittent nitrate therapy in angina pectoris.

¹Department of Medicine, Hospital of the University of Pennsylvania School of Medicine, Philadelphia 19104.

European Heart Journal

|May 1, 1989

Summary

Nitrate tolerance, a reduced response to nitroglycerin, impacts chronic stable angina treatment. Intermittent nitrate therapy aims to overcome this tolerance, improving therapeutic efficacy in patients.

Area of Science:

Pharmacology
Cardiovascular Medicine
Toxicology

Background:

Nitrate tolerance, initially observed as headache tolerance in industrial toxicology, is a phenomenon where the body adapts to nitroglycerin, reducing its effects.
Vascular smooth muscle tolerance to nitroglycerin-induced relaxation was defined in vitro, with reversibility demonstrated.
Potential molecular mechanisms include sulfhydryl group depletion and reduced S-nitrosothiol formation, impacting cyclic GMP activation.

Purpose of the Study:

To explain the rationale for intermittent nitrate therapy based on nitroglycerin tolerance.
To review the pathophysiology of nitrate tolerance and its impact on therapeutic efficacy.
To discuss the diurnal pattern of symptoms in chronic stable angina patients.

Main Methods:

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Review of historical observations and in vitro studies on nitroglycerin tolerance.
Discussion of proposed molecular mechanisms, including sulfhydryl depletion.
Analysis of in vivo studies demonstrating tolerance to oral, transdermal, and intravenous nitrates.

Main Results:

Nitrate tolerance affects the therapeutic efficacy of long-acting nitrates, a finding initially met with skepticism but now widely demonstrated.
Tolerance to antianginal effects can develop within 24 hours with constant plasma concentrations.
The severity of nitrate tolerance varies significantly among individuals.

Conclusions:

Intermittent nitrate therapy is a strategy to mitigate nitroglycerin tolerance.
Understanding nitrate tolerance is crucial for optimizing treatment of chronic stable angina.
Further research into individual variability in tolerance development is warranted.