Qian Yan-Fei, Wang Yang, Tian Wei-Wei, Wang Sheng, Zhao Lei, Li Li, Ma Ke-Tao, Si Jun-Qiang
Department of Physiology, Shihezi University Medical College, Shihezi, Xinjiang 832002, P.R. China.
Mol Med Rep. 2017 Sep;16(3):2620-2626. doi: 10.3892/mmr.2017.6881. Epub 2017 Jun 29.
The current study observed the effects and investigated the mechanism of remifentanil (RMF) on the isolated cerebral basilar arteries of spontaneously hypertensive rats (SHR) and Wistar‑Kyoto (WKY) rats. A pressure myograph system was used to observe and compare the effects of different concentrations of RMF (10‑10‑10‑5 mol/l) on the diameter changes of freshly isolated cerebral basilar arteries, which have been pre‑shrunk by phenylephrine (PE), an endothelium‑independent vasoconstrictor. Vascular smooth‑muscle cells of the cerebral basilar artery (BASMCs) were freshly obtained via enzymolysis. BKCa (large‑conductance calcium‑activated potassium channels) current (IBKCa) and Kv (voltage‑gated potassium channels) current (IKv) were recorded using a whole‑cell patch‑clamp technique. The changes in IBKCa and IKv produced by different concentrations of RMF (10‑10 to 10‑5 mol/l) on the two types of rats with the holding potential of ‑40 mV were observed and compared. The cerebral basilar arteries of the SHR and WKY rats were relaxed by RMF in a concentration-dependent manner (P<0.05; n=5). At the same concentration, the diastolic effect of RMF on SHR was weaker than that observed in WKY rats (P<0.05, n=5). When the rats were pre‑perfused with 10‑3 mol/l of the BKCa channel blocker tetraethylammonium (TEA), the diastolic amplitudes of RMF in SHR and WKY rats were decreased, and the fitting curves shifted down (P<0.05; n=7 and 6, respectively). However, no statistically significant difference was observed with 10‑3 mol/l of the Kv channel blocker 4‑aminopyridine (4‑AP; n=6 and 9, respectively; P>0.05). Outward currents were increased by RMF in both BASMCs of SHR and WKY rats in a voltage‑ and dose‑dependent manner (P<0.05; n=6). At the same concentration, the effect of RMF on the outward currents in BASMCs of WKY rats was stronger than that on SHR (P<0.05; n=6). The enhancing effect of RMF can be partially blocked by either 10‑3 mol/l TEA (P<0.05; n=6) or 10‑3 mol/l 4‑AP (P<0.05 or 0.01; n=6 and 9, respectively) however can be totally blocked by the mixture of TEA and 4‑AP (P<0.05, n=7). RMF served a diastolic role in the cerebral basilar arteries of rats in a dose‑dependent manner, likely by activating the BKCa and Kv channels. However, SHR demonstrated a less pronounced diastolic reaction to RMF than that observed in WKY rats.
本研究观察了瑞芬太尼（RMF）对自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠离体脑基底动脉的作用，并探讨其机制。采用压力肌动描记系统，观察并比较不同浓度的RMF（10⁻¹⁰ - 10⁻⁵ mol/L）对苯肾上腺素（PE，一种不依赖内皮的血管收缩剂）预收缩后的新鲜离体脑基底动脉直径变化的影响。通过酶解新鲜获取脑基底动脉血管平滑肌细胞（BASMCs）。采用全细胞膜片钳技术记录大电导钙激活钾通道（BKCa）电流（IBKCa）和电压门控钾通道（Kv）电流（IKv）。观察并比较不同浓度的RMF（10⁻¹⁰至10⁻⁵ mol/L）在 - 40 mV的钳制电位下对两种大鼠的BASMCs产生的IBKCa和IKv变化。RMF使SHR和WKY大鼠的脑基底动脉呈浓度依赖性舒张（P<0.05；n = 5）。在相同浓度下，RMF对SHR的舒张作用弱于WKY大鼠（P<0.05，n = 5）。当大鼠预先灌注10⁻³ mol/L的BKCa通道阻滞剂四乙铵（TEA）时，SHR和WKY大鼠中RMF的舒张幅度降低，拟合曲线下移（P<0.05；分别为n = 7和6）。然而，10⁻³ mol/L的Kv通道阻滞剂4-氨基吡啶（4-AP）未观察到统计学显著差异（分别为n = 6和9；P>0.05）。RMF使SHR和WKY大鼠的BASMCs外向电流均呈电压和剂量依赖性增加（P<0.05；n = 6）。在相同浓度下，RMF对WKY大鼠BASMCs外向电流的作用强于SHR（P<0.05；n = 6）。RMF的增强作用可被10⁻³ mol/L的TEA（P<0.05；n = 6）或10⁻³ mol/L的4-AP（分别为P<0.05或0.01；n = 6和9）部分阻断，但可被TEA和4-AP的混合物完全阻断（P<0.05，n = 7）。RMF可能通过激活BKCa和Kv通道，以剂量依赖性方式在大鼠脑基底动脉中发挥舒张作用。然而，SHR对RMF的舒张反应不如WKY大鼠明显。
