PT  - JOURNAL ARTICLE
AU  - Yin, Jie
AU  - Wang, Ye
AU  - Han, Weizhong
AU  - Ge, Weili
AU  - Yu, Qingxia
AU  - Jing, Yanyan
AU  - Yan, Wenju
AU  - Liu, Qian
AU  - Gong, Liping
AU  - Yan, Suhua
AU  - Wang, Shuanglian
AU  - Li, Xiaolu
AU  - Li, Yan
AU  - Hu, Hesheng
TI  - Oxytocin Attenuates Sympathetic Innervation with Inhibition of Cardiac Mast Cell Degranulation in Rats after Myocardial Infarction
AID  - 10.1124/jpet.124.002064
DP  - 2024 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 240--249
VI  - 390
IP  - 2
4099  - http://jpet.aspetjournals.org/content/390/2/240.short
4100  - http://jpet.aspetjournals.org/content/390/2/240.full
SO  - J Pharmacol Exp Ther2024 Aug 01; 390
AB  - Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) after myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein. Mast cells accumulated significantly in peri-infarcted tissues and were present in a degranulated state. They expressed OT receptor (OTR), and OT infusion reduced the number of degranulated cardiac mast cells post-MI. Sympathetic hyperinnervation was attenuated as assessed by immunofluorescence for tyrosine hydroxylase (TH). Seven days post-MI, the arrhythmia score of programmed electrical stimulation was higher in vehicle-treated rats with MI than in rats treated with OT. An in vitro study showed that OT stabilized mast cells via the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Further in vivo studies on OTR-deficient mice showed worsening mast cell degranulation and worsening sympathetic innervation. OT pretreatment inhibited cardiac mast cell degranulation post-MI and prevented sympathetic hyperinnervation, along with mast cell stabilization via the PI3K/Akt pathway.SIGNIFICANCE STATEMENT This is the first study to elucidate the role and mechanism of oxytocin (OT) in inflammatory-sympathetic communication mediated sympathetic hyperinnervation after myocardial infarction (MI), providing new approaches to prevent fatal arrhythmias.