Does chronic nitrate therapy induce tolerance to short-acting ones?

Area of Science:

• Cardiology
• Pharmacology

Background:

• Nitrate tolerance is a known phenomenon that can reduce the effectiveness of nitrate therapy.
• Understanding nitrate tolerance is crucial for managing patients with stable angina.

Purpose of the Study:

• To investigate whether long-term administration of isosorbide dinitrate (ISDN) or molsidomine leads to tolerance to short-acting nitrates.
• To assess the impact of high-dose long-acting nitrates on the efficacy of short-acting nitrates in angina patients.

Main Methods:

• 14 male patients with stabilized angina (IIIrd degree) underwent stress tests.
• Patients received either ISDN (120 mg/day) or molsidomine (16 mg/day) long-term, with treatments interchanged every 6 weeks.
• Stress tests were performed before and after administration of short-acting ISDN (2.5 mg) during both long-term therapy periods.

Main Results:

• Short-acting nitrate administration significantly increased exercise tolerance (time to maximal load) in all patients, both at baseline and during long-term ISDN or molsidomine therapy.
• The increase in exercise tolerance after short-acting nitrate was comparable between baseline and long-term therapy periods.
• No evidence of nitrate tolerance was observed in patients receiving long-term ISDN or molsidomine therapy.

Conclusions:

• Long-term administration of high-dose ISDN or molsidomine does not induce tolerance to the effects of short-acting nitrates in patients with stable angina.
• The efficacy of short-acting nitrates remains preserved even during continuous long-term nitrate therapy.