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Biotransformation of organic nitrates to nitric oxide by vascular smooth muscle and endothelial cells.

Abstract：

:The vasodilator action of organic nitrates is thought to be mediated by an increase in the level of cGMP following stimulation of the cytosolic enzyme guanylate cyclase in the vascular smooth muscle cell. However, direct evidence for the formation of the putative active metabolite, nitric oxide (NO) within the different compartments of the vascular wall is still missing. We here demonstrate for the first time that cultured vascular smooth muscle cells as well as endothelial cells from different species actively metabolize organic nitrates to NO. We furthermore present evidence for an outward transport of cGMP from both cell types following stimulation of soluble guanylate cyclase. The rate of NO release closely correlated with the rate of cGMP egression. Biotransformation of organic nitrates to NO appeared to comprise at least two different components, a heat-sensitive enzymatic pathway which is short-lived and prone to rapid desensitization and a second non-enzymatic component which is apparently unsaturable and longer lasting. The marked decrease in the release of NO and cGMP upon the repeated administration of organic nitrates suggests that the phenomenon of "nitrate tolerance" is mainly due to an impaired biotransformation. We propose that the metabolism of nitrates to NO may have important implications for the prevention of atherosclerosis and the therapeutic modulation of blood cell function.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Feelisch M,Kelm M

doi

10.1016/s0006-291x(05)81290-2

subject

Has Abstract

pub_date

1991-10-15 00:00:00

pages

286-93

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)81290-2

journal_volume

180

pub_type

杂志文章

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