Open AccessUpregulation of 5-Hydroxytryptamine Receptor Signaling in Coronary Arteries after Organ Culture
Author(s) -
Chunyu Deng,
Hui Yang,
SuJuan Kuang,
Fang Rao,
Yan Xue,
ZhiLing Zhou,
Xiaoying Li,
ZhiXin Shan,
Xiaohong Li,
Qiaoli Lin,
Shulin Wu,
Xiang Yu
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0107128
Subject(s) - coronary arteries , vasoconstriction , medicine , artery , cardiology , vascular smooth muscle , myograph , constriction , endocrinology , smooth muscle
Background 5-Hydroxytryptamine (5-HT) is a powerful constrictor of coronary arteries and is considered to be involved in the pathophysiological mechanisms of coronary-artery spasm. However, the mechanism of enhancement of coronary-artery constriction to 5-HT during the development of coronary artery disease remains to be elucidated. Organ culture of intact blood-vessel segments has been suggested as a model for the phenotypic changes of smooth muscle cells in cardiovascular disease. Methodology/Principal Findings We wished to characterize 5-HT receptor-induced vasoconstriction and quantify expression of 5-HT receptor signaling in cultured rat coronary arteries. Cumulative application of 5-HT produced a concentration-dependent vasoconstriction in fresh and 24 h-cultured rat coronary arteries without endothelia. 5-HT induced greater constriction in cultured coronary arteries than in fresh coronary arteries. U46619- and CaCl 2 -induced constriction in the two groups was comparable. 5-HT stimulates the 5-HT 2A receptor and cascade of phospholipase C to induce coronary vasoconstriction. Calcium influx through L-type calcium channels and non-L-type calcium channels contributed to the coronary-artery constrictions induced by 5-HT. The contractions mediated by non-L-type calcium channels were significantly enhanced in cultured coronary arteries compared with fresh coronary arteries. The vasoconstriction induced by thapsigargin was also augmented in cultured coronary arteries. The decrease in Orai1 expression significantly inhibited 5-HT-evoked entry of Ca 2+ in coronary artery cells. Expression of the 5-HT 2A receptor, Orai1 and STIM1 were augmented in cultured coronary arteries compared with fresh coronary arteries. Conclusions An increased contraction in response to 5-HT was mediated by the upregulation of 5-HT 2A receptors and downstream signaling in cultured coronary arteries.