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Chloroquine differentially modulates coronary vasodilation in control and diabetic mice.
- Source :
- British Journal of Pharmacology; Jan2020, Vol. 177 Issue 2, p314-327, 14p, 3 Charts, 4 Graphs
- Publication Year :
- 2020
-
Abstract
- <bold>Background and Purpose: </bold>Chloroquine is a traditional medicine to treat malaria. There is increasing evidence that chloroquine not only induces phagocytosis but regulates vascular tone. Few reports investigating the effect of chloroquine on vascular responsiveness of coronary arteries have been made. In this study, we examined how chloroquine affected endothelium-dependent relaxation in coronary arteries under normal and diabetic conditions.<bold>Experimental Approach: </bold>We isolated coronary arteries from mice and examined endothelium-dependent relaxation (EDR). Human coronary endothelial cells and mouse coronary endothelial cells isolated from control and diabetic mouse (TALLYHO/Jng [TH] mice, a spontaneous type 2 diabetic mouse model) were used for the molecular biological or cytosolic NO and Ca2+ measurements.<bold>Key Results: </bold>Chloroquine inhibited endothelium-derived NO-dependent relaxation but had negligible effect on endothelium-derived hyperpolarization (EDH)-dependent relaxation in coronary arteries of control mice. Chloroquine significantly decreased NO production in control human coronary endothelial cells partly by phosphorylating eNOSThr495 (an inhibitory phosphorylation site of eNOS) and attenuating the rise of cytosolic Ca2+ concentration after stimulation. EDR was significantly inhibited in diabetic mice in comparison to control mice. Interestingly, chloroquine enhanced EDR in diabetic coronary arteries by, specifically, increasing EDH-dependent relaxation due partly to its augmenting effect on gap junction activity in diabetic mouse coronary endothelial cells.<bold>Conclusions and Implications: </bold>These data indicate that chloroquine affects vascular relaxation differently under normal and diabetic conditions. Therefore, the patients' health condition such as coronary macrovascular or microvascular disease, with or without diabetes, must be taken account into the consideration when selecting chloroquine for the treatment of malaria. [ABSTRACT FROM AUTHOR]
- Subjects :
- GLYCEMIC control
CHLOROQUINE
PHAGOCYTOSIS
CORONARY arteries
VASODILATION
ENDOTHELIAL cells
BIOLOGICAL models
ENDOTHELIUM
CELL membranes
ANIMAL experimentation
TYPE 2 diabetes
CELLULAR signal transduction
VASODILATORS
RESEARCH funding
ANTIMALARIALS
OXIDOREDUCTASES
NITRIC oxide
MICE
PHOSPHORYLATION
ANIMALS
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 177
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 141473136
- Full Text :
- https://doi.org/10.1111/bph.14864