Upregulation of Phosphodiesterase 1A1 Expression Is Associated With the Development of Nitrate Tolerance | Zendy

DongSoo Kim | Zendy; Sergei D. Rybalkin | Zendy; Xinchun Pi | Zendy; Yining Wang | Zendy; Changxi Zhang | Zendy; Thomas Münzel | Zendy; Joseph A. Beavo | Zendy; Bradford C. Berk | Zendy; Chen Yan | Zendy

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Upregulation of Phosphodiesterase 1A1 Expression Is Associated With the Development of Nitrate Tolerance

Author(s) -

DongSoo Kim,

Sergei D. Rybalkin,

Xinchun Pi,

Yining Wang,

Changxi Zhang,

Thomas Münzel,

Joseph A. Beavo,

Bradford C. Berk,

Chen Yan

Publication year - 2001

Publication title -

circulation

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 7.795

H-Index - 607

eISSN - 1524-4539

pISSN - 0009-7322

DOI - 10.1161/hc4401.098432

Subject(s) - vasodilation , nitric oxide , phosphodiesterase , downregulation and upregulation , phosphodiesterase 3 , western blot , soluble guanylyl cyclase , pharmacology , vasoconstriction , endocrinology , medicine , intracellular , chemistry , biochemistry , enzyme , cyclic gmp , gene

The efficacy of nitroglycerin (NTG) as a vasodilator is limited by tolerance, which develops shortly after treatment begins. In vascular smooth muscle cells (VSMCs), NTG is denitrated to form nitric oxide (NO), which activates guanylyl cyclase and generates cGMP. cGMP plays a key role in nitrate-induced vasodilation by reducing intracellular Ca(2+) concentration. Therefore, one possible mechanism for development of nitrate tolerance would be increased activity of the cGMP phosphodiesterase (PDE), which decreases cGMP levels.

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