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We determined membrane actions of nonsteroidal anti-inflammatory drug flufenamic acid (FFA) and a related derivative niflumic acid (NFA), on gap junction intercellular communication among vascular smooth muscle cells (VSMC) in situ of acutely isolated arteriole segments from the spiral modiolar artery (SMA), anterior inferior cerebellar artery (AICA) and mesenteric artery (MA), and non-junctional membrane channels in dispersed VSMCs.Whole-cell electrical recordings were made from VSMCs embedded or dissociated from guinea pig SMA, AICA and MA segments.FFA concentration-dependently and reversibly suppressed the input conductance(Ginput) or increased the input resistance (Rinput), with an IC50 of 26, 33 and 56 μM in in situ of acutely isolated SMA,AICA and MA segments, respectively;The differences among the three arterioles in IC50s were not statistically significant.A complete electrical isolation of the recorded VSMC was normally reached at ≥300 μM.NFA had a similar action on gap junction among VSMCs with an IC50 of 40, 48 and 62 μM in SMA, AICA and MA segments respectively.On dispersed VSMCs, FFA and NFA concentration-dependently increased the delayed rectifier potassium current (KDR), with a similar EC50 of ~300 μM for both FFA and NFA in the three vessels.Iberiotoxin could remarkably inhibit the enhancement of the KDR by FFA and NFA.We conclude that FFA and NFA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at ≥300 μM;no significant difference was observed among the three arterioles for the gap junction blockade potency, suggesting a homogeneous property of the gap junctions in SMA, MA and AICA.FFA and NFA also activate BKCa channel on dispersed VSMCs in the three arterioles.