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

Abstract

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.