Substance P/neurokinin1 receptor is associated with the expression of cardiac stem/pluripotency-associated genes in diabetic right and left atria

Substance P (SP) is a cardioprotective neuropeptide that interacts with the G protein-coupled neurokinin-1 receptor (NK1R). Although the expression of SP/NK1R in the right atrium (RA) of diabetic patients is known to be significantly impaired, the molecular mechanism remains unclear. LETO and OLETF rats were randomly divided into 3 groups: saline, SP injection (5 nmole/kg), and SP+RP injection (1 mg/kg RP67580, a selective non-peptide tachykinin NK1R antagonist). After 3 weeks, the left atrium (LA), RA, and left ventricle (LV) of the rats were collected. Cardiac stem/pluripotency-associated genes in the diabetic atria of each group were comprehensively examined using qRT-PCR analysis. qRT-PCR analysis demonstrated that only the RA of SP-treated OLETF rats exhibited significantly higher levels of alpha-SMA, GATA4, TBX5, and Klf4 in the mRNA, compared to the control. RP prevented the expression of NK1R and four SP-associated genes in the RA of SP-treated OLETF rats. In conclusion, our findings provide novel mechanistic insights into the role of NK1R in diabetic atria.