Effects of RMF on BKCa and Kv channels in basilar arterial smooth-muscle cells of SHR

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 (I(BKCa)) and Kv (voltage-gated potassium channels) current (I(Kv)) were recorded using a whole-cell patch-clamp technique. The changes in I(BKCa) and I(Kv) 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.