Clinical aspects of nitrate tolerance.

Tolerance to the organic nitrates is a vexing problem. Tolerance is clearly avoidable with the employment of appropriate and well-designed dosing regimes, utilizing fewer doses and/or a nitrate-free interval. The emerging story of thiol donors and ACE inhibition to prevent tolerance is as yet incomplete. Hopefully, future research will provide the clinician with additional modalities to eliminate the threat of nitrate attenuation. The organic nitrates are superb drugs whose potential usefulness in cardiovascular medicine is clearly limited by nitrate tolerance. While the mechanisms involved in producing vascular smooth muscle attenuation are complex and multiple, it appears that we will be able to resolve this problem in the future, increasing the remarkable benefits of these drugs for patients around the world.