Key result
Organ culture enhances coronary vasoconstriction ~48% to 5-HT via upregulated 5-HT2A receptors.
Why the study?
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 rat coronary arteries enhances 5-HT-induced vasoconstriction via upregulation of 5-HT2A receptors and downstream calcium signaling pathways.
Organ culture upregulates 5-HT2A signaling and 5-HT constriction in rat coronaries; supports disease model but leaves clinical relevance open.
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 CaCl2-induced constriction in the two groups was comparable. 5-HT stimulates the 5-HT2A 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 Ca2+ in coronary artery cells. Expression of the 5-HT2A 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-HT2A receptors and downstream signaling in cultured coronary arteries.
No takes yet. Share an insight, caveat, or question.
Deng et al. (2014) studied Coronary artery disease model. Organ culture vs. Fresh coronary arteries was evaluated on Maximal contraction (Emax) induced by 5-HT (p=<0.01). Organ culture of rat coronary arteries for 24 hours significantly increased 5-HT-induced maximal vasoconstriction compared to fresh arteries (204.2% vs 138.3%, p<0.01) via upregulation of 5-HT2A receptors.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: