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Chloroquine Attenuates Endothelium‐dependent Relaxation in Mouse Coronary Artery
Author(s) -
Zhang Qian,
Wang Jian,
Makino Ayako
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.837.15
Subject(s) - apamin , endothelium , myograph , pharmacology , chemistry , relaxation (psychology) , medicine , cardiotoxicity , anesthesia , endocrinology , potassium channel , toxicity
Chloroquine (CQ) is widely used as an antimalarial drug and it is also effective in treating the symptoms of lupus. It has been reported that CQ exhibits cardiotoxicity and has an adverse effect on nerve system by overdose or prolonged treatment of CQ. However, little is known about the effect of CQ on cardiovascular system. This study was designed to examine the effect of CQ on vascular relaxation in coronary artery. Third‐ or fourth‐order small coronary arteries were dissected from mice and the rings were mounted in a wire myograph with 20μm wires. Endothelium‐dependent relaxation was conducted by ACh administration in a dose‐dependent manner. Endothelium‐derived hyperpolarization (EDH)‐dependent relaxation was observed by inhibition of NO (via L‐NAME, 100 μmol/L) and prostacyclin (via indomethacin, 10 μmol/L) during ACh‐induced relaxation. A cocktail of apamin (100 nmol/L) and TRAM34 (10 μmol/L) was used to inhibits EDH‐dependent relaxation. CQ (10 μmol/L) was treated for 30 min before vascular constriction by PGF2α. CQ significantly inhibited endothelium‐dependent relaxation compared to the control (vehicle treatment), whereas CQ had no effect on sodium nitroprusside‐induced relaxation (endothelium‐independent relaxation). Interestingly, EDH‐dependent relaxation was markedly enhanced by the pretreatment of CQ compared to the vehicle pretreatment. ACh‐induced relaxation was diminished in the presence of L‐NAME, indomethacin, apamin, and TRAM34. These data suggest that CQ might inhibit endothelium‐dependent relaxation via, at least in part, the decrease in NO production and/or NO bioavailability in endothelial cells, but not due to altering EDH‐dependent relaxation. Support or Funding Information NIH/HL115578