Spinal neuronal NOS activation mediates intrathecal fentanyl preconditioning induced remote cardioprotection in rats

Fentanyl has been widely used in anesthesia and analgesia, especially for cardiovascular surgeries. The aim of the study was to evaluate whether remote intrathecal fentanyl preconditioning (RFPC) provides cardioprotection and the role of spinal nitric oxide synthase (NOS) system in this effect. Fentanyl (0.3μg/kg) was administered intrathecally during RFPC by 3 cycles of 5-minute infusions interspersed with 5-minute infusion free periods. A non-specific nitric oxide synthase (NOS) inhibitor NG-nitro l-arginine methyl ester (l-NAME, 30 nmol) and a selective nNOS inhibitor 7-nitroindazole (7-NI, 100 nmol) were administered intrathecally 10 min before RFPC, and were used to evaluate the involvement of the NOS system of the spinal cord. RFPC group markedly reduced the infarct size compared with control. However, the cardioprotection of RFPC could be abolished by pretreatment with l-NAME and 7-NI. RFPC merely increased the expression of nNOS and did not affect iNOS and eNOS expression. l-NAME reversed nNOS expression up-regulation induced by RFPC treatment. The present study demonstrated that RFPC effectively induced cardioprotection through activating the nNOS in the spinal cord.