Chloroquine differentially modulates coronary vasodilation in control and diabetic mice.
Br J Pharmacol
; 177(2): 314-327, 2020 01.
Article
in English
| MEDLINE | ID: covidwho-613365
ABSTRACT
BACKGROUND AND PURPOSE:
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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. CONCLUSIONS AND IMPLICATIONS 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Vasodilation
/
Vasodilator Agents
/
Endothelium, Vascular
/
Chloroquine
/
Coronary Vessels
/
Diabetes Mellitus, Type 2
/
Antimalarials
Topics:
Traditional medicine
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Br J Pharmacol
Year:
2020
Document Type:
Article
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