Chaytor Andrew T, Taylor Hannah J, Griffith Tudor M
Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom.
Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1548-55. doi: 10.1152/ajpheart.00903.2001.
We have compared the mechanisms that contribute to endothelium-derived hyperpolarizing factor (EDHF)-type responses induced by ACh and the Ca(2+) ionophore A-23187 in the rabbit iliac artery. Relaxations to both agents were associated with ~1.5-fold elevations in smooth muscle cAMP levels and were attenuated by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA) and potentiated by the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Mechanical responses were inhibited by coadministration of the Ca(2+)-activated K(+) channel blockers apamin and charybdotoxin, both in the absence and presence of IBMX, but were unaffected by blockade of ATP-sensitive K(+) channels with the sulphonylurea glibenclamide. Relaxations and elevations in cAMP evoked by ACh were abolished by 18alpha-glycyrrhetinic acid, which disrupts gap junction plaques, whereas the corresponding responses to A-23187 were unaffected by this agent. Consistently, in "sandwich" bioassay experiments, A-23187, but not ACh, elicited extracellular release of a factor that evoked relaxations that were inhibited by DDA and potentiated by IBMX. These findings provide evidence that EDHF-type relaxations of rabbit iliac arteries evoked by ACh and A-23187 depend on cAMP accumulation in smooth muscle, but involve signaling via myoendothelial gap junctions and the extracellular space, respectively.
我们比较了乙酰胆碱（ACh）和钙离子载体A-23187在兔髂动脉中诱导内皮源性超极化因子（EDHF）型反应的机制。两种药物引起的舒张均与平滑肌中环磷酸腺苷（cAMP）水平升高约1.5倍有关，且被腺苷酸环化酶抑制剂2'，5'-二脱氧腺苷（DDA）减弱，并被cAMP磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）增强。在有无IBMX的情况下，机械反应均被同时给予的钙激活钾通道阻滞剂蜂毒明肽和大蝎毒素抑制，但不受磺酰脲类格列本脲阻断ATP敏感性钾通道的影响。ACh引起的舒张和cAMP升高被破坏缝隙连接斑的18α-甘草次酸消除，而对A-23187的相应反应不受该药物影响。同样，在“三明治”生物测定实验中，A-23187而非ACh引起一种因子的细胞外释放，该因子引起的舒张被DDA抑制并被IBMX增强。这些发现提供了证据，表明ACh和A-23187引起的兔髂动脉EDHF型舒张分别依赖于平滑肌中的cAMP积累，但分别涉及通过肌内皮缝隙连接和细胞外空间的信号传导。
