Biochemical mechanism of organic nitrate action

Ho Leung Fung, Suk Jae Chung, John Anthony Bauer, Saeho Chong, Elizabeth A. Kowaluk

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Increasing evidence suggests that organic nitrate action derives from their metabolic conversion to nitric oxide (NO) in the vascular smooth muscle cell. The primary catalytic activity of this process appears to reside at the cellular plasma membrane. There is no concrete evidence to indicate that NO formation is preceded by the production of inorganic nitrite ion or that the NO produced needs to form S-nitrosothiols before it can activate guanylate cyclase to produce cyclic guanosine 3′,5′-monophosphate (cGMP). Although sulfhydryl donors can partially reverse nitroglycerin-induced tolerance in patients, this phenomenon (by itself) is not sufficient to implicate intracellular sulfhydryl depletion as an operating mechanism of clinical nitrate tolerance. This is because sulfhydryl donors can react with nitroglycerin extracellularly to form S-nitrosothiols, and nonsulfhydryl compounds, such as enalapril and hydralazine, can prevent the development of in vivo nitrate tolerance. In addition to the cellular biochemical reactions, organic nitrates also produce systemic biochemical effects through altering neurohormonal status. These systemic effects may contribute significantly to the development of nitrate tolerance in therapeutic situations.

Original languageEnglish
Pages (from-to)B4-B10
JournalAmerican Journal of Cardiology
Volume70
Issue number8
DOIs
StatePublished - Sep 24 1992

Bibliographical note

Funding Information:
From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Buffalo, New York. This work was supported in part by grants HL22273 and GM42850 from the National Institutes of Health, Bethesda, Maryland.

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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