Opioid-Induced Preconditioning Is Dependent on Caveolin-3 Expression

Caveolae are flask‐like invaginations of the sarcolemmal membrane. Recently, we have shown that caveolar structural proteins, caveolins, are essential in cardiac protection and that cardiac specific overexpression of caveolin‐3 (Cav‐3 OE) results in innate cardiac protection. Additionally, we identified that opioid‐induced preconditioning (OPC) is absent when caveolae are disrupted in vitro. However, the impact of caveolin‐3 and caveolae on OPC in vivo has not been investigated. 8‐12 week old Cav‐3 OE, caveolin‐3 knockout mice (Cav‐3 KO), and control mice were exposed to 30 min ischemia/2 hr reperfusion (I/R). Cav‐3 OE and control mice were treated with naloxone, a non‐selective opioid antagonist, 10 min prior to I/R to determine whether basal protection was abolished. Cav‐3 KO and control mice were treated with SNC, a delta‐selective opioid agonist 15 min prior to I/R to induce OPC. Cav‐3 OE mice displayed endogenous cardiac protection from I/R when compared to control mice (20±2% vs. 41±2%, n=8, respectively). This endogenous protection in Cav‐3 OE mice was abolished with naloxone pretreatment (41±2%). Conversely, control mice were protected in the presence of SNC (28±1%), although no protection was observed in Cav‐3 KO mice (38±5%). These results suggest that OPC is dependent on caveolin‐3 expression and endogenous protection induced in Cav‐3 OE mice may be opioid dependent.