κ-opioid receptor is involved in the cardioprotection induced by exercise training

Abstract

The present study was designed to test the hypothesis that exercise training elicited a cardioprotective effect against ischemia and reperfusion (I/R) via the κ-opioid receptor (κ-OR)-mediated signaling pathway. Rats were randomly divided into four groups: the control group, the moderate intensity exercise (ME) group, the high intensity exercise (HE) group, and the acute exercise (AE) group. For the exercise training protocols, the rats were subjected to one week of adaptive treadmill training, while from the second week, the ME and HE groups were subjected to eight weeks of exercise training, and the AE group was subjected to three days of adaptive treadmill training and one day of vigorous exercise. After these protocols, the three exercise training groups were divided into different treatment groups, and the rats were subjected to 30 min of ischemia and 120 min of reperfusion. Changes in infarct size and serum cTnT (cardiac troponin T) caused by I/R were reduced by exercise training. Moreover, cardiac dysfunction caused by I/R was also alleviated by exercise training. These effects of exercise training were reversed by nor-BNI (a selective κ-OR antagonist), Compound C (a selective AMPK inhibitor), Akt inhibitor and L-NAME (a non-selective eNOS inhibitor). Expression of κ-OR and phosphorylation of AMPK, Akt and eNOS were significantly increased in the ME, HE and AE groups. These findings demonstrated that the cardioprotective effect of exercise training is possibly mediated by the κ-OR-AMPK-Akt-eNOS signaling pathway.

Prediction of putative small molecules for manipulation of enriched signalling pathways in hESC-derived early cardiovascular progenitors by bioinformatics analysis

“…It is shown that administration of KOR agonists can improve cardiac performance after myocardial infarction due to increased expression of myocardial haem oxygenase through the activity of PI3K/Akt signalling pathway [55 ]. The modulatory effect of KOR agonist on Akt signalling pathway has been approved in other contexts [56, 57 ]. Interestingly, the cross‐talks between GSK3 (one of the downstream mediators of Wnt signalling pathway), Akt, and KOR agonists have been shown in cardiac protection induced by remote electro‐stimulation [58 ].…”

κ-opioid receptor stimulation alleviates rat vascular smooth muscle cell calcification via PFKFB3-lactate signaling

“…As a selective agonist of κ-OR, U50,488H can improve hemodynamics and vascular endothelial function and reverse vascular remodeling by activating cardiovascular κ-OR [ 28 – 30 ]. Previous studies have confirmed that a higher dose of U50,488H significantly prevented the myocardial ischemia and reperfusion (I/R) injury-induced increase in myocardial lipid peroxidation and depletion of myocardial antioxidants and that κ-OR stimulation exerts a protective effect on vascular endothelium [ 31 , 32 ]. However, the impact of κ-OR stimulation on vascular remodeling during VC remains elusive.…”