Nitrite reverses nitroglycerin tolerance via repletion of a nitrodilator-activated nitric oxide store in vascular smooth muscle cells.

ABSTRACT: Repeated use of nitroglycerin results in a loss of its vasodilatory efficacy which limits its clinical use for the treatment of angina pectoris. This tolerance phenomenon is a defining characteristic of all compounds classified as nitrodilators, which includes NTG as well as S-nitrosothiols and dinitrosyl iron complexes. These compounds vasodilate via activation of soluble guanylate cyclase, although they do not release requisite amounts of free nitric oxide (NO) and some do not even cross the plasma membrane. Here we demonstrate that nitrodilators cause vasodilation via mobilization of NO moiety from a nitrodilator-activated NO store (NANOS) pre-formed in the vascular smooth muscle cell, similar to the mechanism by which UV light is also known to cause vasodilation and tolerance. Intraper

SUBMITTER: Liu T 

PROVIDER: S-EPMC11815961 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature