The Effect Of Remifentanil On BK_Ca And K_v Channels In Basilar Arterial Smooth Muscle Cells Of Spontaneously Hypertensive Rats

Objective: The aim of this study is to observe the effects of remifentanil（RMF） on isolated cerebral basilar artery of spontaneously hypertensive rats（SHR） and Wistar-Kyoto（WKY） rats, and then investigate the mechanism.Methods: Pressure myograph system was used to observe and compare with the diameter changes of different concentrations of RMF（10-10¹0-5 mol/L） on freshly isolated cerebral basilar artery, which is pre-shrunk by Phenylephrine（PE, endothelium independent vasoconstrictor）. BASMCs were obtained freshly by the method of enzymolysis. BK_Ca current(IBK_Ca) and Kv current（Ikv） was recorded by the whole-cell patch clamp technique. The changes in IBK_Ca and Ikv were observed and compared with, which was produced by different concentrations of RMF（10-10¹0-5 mol/L） on two kind rats with the holding potential of-40 m V. Then channel blockerwere given to identify the type of channel.Results: 1)Cerebral basilar artery was relaxed by RMF in a concentration-dependent manner（P < 0.05,n=5）.2) Compared to WKY rats, the diastolic effect of RMF on SHR was weaker at the same concentration（P <0.05, n=5）.3) Pre-perfused by 10-3 mol/L tetraethylammonium(TEA, BK_Ca channel blocker), the diastolic amplitudes of RMF on SHR and WKY rats significantly decreased（P < 0.05, n=7 and 6）, which indicated that that cerebral basilar artery of SHR and WKY rats were relaxed by RMF were mediated by BK_Ca channel.4) Giving 10-3 mol/L 4-aminopyridine（4-AP, Kv channel blocker）, different concentration of RMF also relaxed cerebral basilar artery of SHR and WKY rats in a dose-dependent manner, but compared without4-AP, the diastolic amplitudes was similar（P > 0.05, n=6 and 9）.5) With-40 m V of single BASMCs holding potential, outward currents were increased in the range of 20⁶0 m V by RMF in both BASMCs of SHR and WKY rats in a voltage-dependent manner（P < 0.05, n=6）.6) Under the effect of RMF at the concentration of 10-10, 10-9, 10-8, 10-7, 10-6 and 10-5 mol/L, compared to pre-administration, outward current in BASMCs of SHR rats was increased in a dose-dependent manner,except 10-10 mol/L; while WKY rats in all concentration.7) The effect of RMF on outward currents in BASMCs of WKY rats was stronger than SHR at the concentration of 10-9, 10-8 and 10-7 mol/L（P < 0.05, n=6）.8) The enhancing effect of RMF can be partially blocked by 10-3mol/L TEA（P < 0.05, n=6）, which indicated the outward current in BASMCs of SHR and WKY rats increased by RMF was possibly mediated by BK_Ca channel.9) The enhancing effect of RMF can be partially blocked by 10-3 mol/L 4-AP（P < 0.05, n=6）, which showed the outward current possibly mediated by Kv channel was participated in the current in BASMCs of SHR and WKY rats increased by RMF.10) The enhancing effect of RMF can be totally blocked by the mixture of 10-3 mol/L TEA and 4-AP（P <0.05, n=7 and 6）, which described the outward current in BASMCs of SHR and WKY rats increased by RMF was collectively mediated by BK_Ca and Kv channel.Conclusion: RMF played a diastolic role in cerebral basilar artery of rats in a dose-dependent manner,probably by activating BK_Ca and Kv channels, and SHR had a less diastolic reaction to RMF than WKY rats.