Favaloro Joanne L, McPherson Grant A
Department of Pharmacology, Monash University, 3800 Clayton, Victoria, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Apr;369(4):367-73. doi: 10.1007/s00210-004-0879-8. Epub 2004 Mar 19.
This study characterises the vasorelaxation and hyperpolarisation effects of the negatively charged quaternary compound tetraphenylboron (TPB) in the rat small mesenteric artery. Segments of rat small mesenteric artery were mounted in a myograph and vessel tone and membrane potential were measured simultaneously. In vessels pre-contracted with vasopressin (0.3-0.6 nM), U46619 (30-90 nM) or methoxamine (0.3-3 microM), TPB (0.1-100 microM) produced a marked endothelium-independent relaxation. However, vasorelaxation responses to TPB were abolished in tissues pre-contracted with K(+) (50 mM), and significantly inhibited by glibenclamide (glib, 10 microM). In the absence of tone, TPB (1-30 microM) caused a concentration-dependent membrane hyperpolarisation of rat mesenteric artery smooth muscle cells, which was not dependent on the endothelium, but sensitive to glibenclamide (10 microM). In methoxamine (0.3-3 microM) pre-contracted vessels, the relaxation response was associated with a marked hyperpolarisation, which was also sensitive to glibenclamide (10 microM), further inhibited by a combination of K(+) channel blockers (glib [10 microM], charybdotoxin [100 nM], apamin [100 nM], 4-aminopyridine [1 mM] and Ba(2+) [30 microM]) and abolished by 50 mM K(+). The results of this study show that TPB causes a vasorelaxation and hyperpolarisation response in the rat small mesenteric artery through a direct action on the vascular smooth muscle. TPB exerts its effects partially via the activation of K(ATP) channels, but also by another mechanism involving K(+)-dependent hyperpolarisation.
本研究对带负电荷的季铵化合物四苯基硼(TPB)在大鼠小肠系膜动脉中的血管舒张和超极化作用进行了表征。将大鼠小肠系膜动脉段安装在肌张力测定仪中,同时测量血管张力和膜电位。在预先用血管加压素(0.3 - 0.6 nM)、U46619(30 - 90 nM)或甲氧明(0.3 - 3 μM)预收缩的血管中,TPB(0.1 - 100 μM)产生明显的不依赖内皮的舒张作用。然而,在预先用K⁺(50 mM)预收缩的组织中,对TPB的血管舒张反应被消除,并且被格列本脲(10 μM)显著抑制。在无张力的情况下,TPB(1 - 30 μM)引起大鼠肠系膜动脉平滑肌细胞浓度依赖性的膜超极化,这不依赖于内皮,但对格列本脲(10 μM)敏感。在预先用甲氧明(0.3 - 3 μM)预收缩的血管中,舒张反应与明显的超极化相关,这也对格列本脲(10 μM)敏感,进一步被钾通道阻滞剂组合(格列本脲[10 μM]、蝎毒素[100 nM]、蜂毒明肽[100 nM]、4 - 氨基吡啶[1 mM]和Ba²⁺[30 μM])抑制,并被50 mM K⁺消除。本研究结果表明,TPB通过直接作用于血管平滑肌在大鼠小肠系膜动脉中引起血管舒张和超极化反应。TPB部分通过激活ATP敏感性钾通道发挥其作用,但也通过另一种涉及钾依赖性超极化的机制。