Biotransformation of organic nitrates and vascular smooth muscle cell function

Trends in Pharmacological Sciences
Brian M BennettW C Simon

Abstract

The organic nitrates are interesting examples of drugs that undergo biotransformation at their site of action to generate the active form of the drug. Furthermore, tolerance to the vasodilator effects of organic nitrates is associated with impairment of this metabolic activation process. Despite considerable research effort, the intracellular processes and the chemical reaction pathways by which organic nitrates are converted to their active form are still unresolved. This review by Brian Bennett and colleagues summarizes the characteristics of organic-nitrate biotransformation in vascular smooth muscle, the difficulties encountered when assessing this biotransformation, and the evidence for the role of two identified vascular biotransformation systems (glutathione-S-transferases and the cytochrome P450 system) in the metabolic activation of organic nitrates.

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