Adeagbo A S
Department of Physiology, Biophysics and Center for Applied Microcirculatory Research, School of Medicine, Health Sciences Center, University of Louisville, KY 40292, USA.
Eur J Pharmacol. 1999 Aug 27;379(2-3):151-9. doi: 10.1016/s0014-2999(99)00489-6.
Hyperpolarization of most blood vessels occurs by the opening of K(Ca) channels. 1-Ethyl-2-benzimidazolinone (1-EBIO) is a direct activator of K(Ca) channels in epithelial cells and is potentially valuable for studying cellular hyperpolarization. This study reports the effects of 1-EBIO on isolated rat mesenteric beds perfused with normal (4.7 mM), or high (20 or 80 mM) K+ physiological salt solution (PSS) and constricted with an alpha1-adrenoceptor agonist, cirazoline (0.3-1 microM). Arterial perfusion pressures were decreased by 1-EBIO (0.1-30 nmol) in a dose- and endothelium-dependent manner. Infusion of penitrem A (100 nM), a maxi-K+ channel blocker, or apamin (0.5 microM), a small-conductance (SK(Ca)) K+ channel blocker, produced significant increases in cirazoline-mediated tone (mm Hg): 103.3 +/- 8.7 (control) vs. 156.3 +/- 14.3 (penitrem A); or 93.0 +/- 15.8 (control) vs. 114.0 +/- 15.4 (apamin). 1-EBIO relaxations were attenuated by penitrem A, while apamin, dendrotoxin (50 nM; a Kv channel antagonist), or ouabain (100 microM; a sodium pump blocker) failed to alter the responses. I-EBIO-mediated relaxations decreased significantly with increasing extracellular [K+]: relaxations to 30 nmol were 89.3% +/- 3.2% (4.7 mM K+, normal PSS) vs. 59.5% +/- 3.4% and 19.0% +/- 3.9% for 20 and 80 mM K+ PSS, respectively. Nomega-nitro-L-arginine-methyl ester (L-NAME; 100 microM), and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM), selective inhibitors of nitric oxide synthase, and nitric oxide-sensitive guanylate cyclase, respectively, abolished 1-EBIO relaxations in vessels perfused with 20 or 80 mM K+ PSS. We conclude that: (1) maxi-K+ and SK(Ca) channels are present in rat mesenteric arterial vessels and actively contribute to vascular tone, (2) vasodilator action of 1-EBIO involves the opening of endothelial maxi-K+ channels and nitric oxide synthesis.
大多数血管的超极化是通过大电导钙激活钾通道（K(Ca)通道）的开放实现的。1-乙基-2-苯并咪唑啉酮（1-EBIO）是上皮细胞中K(Ca)通道的直接激活剂，对于研究细胞超极化具有潜在价值。本研究报告了1-EBIO对用正常（4.7 mM）或高（20或80 mM）钾离子生理盐溶液（PSS）灌注并用α1-肾上腺素能受体激动剂西拉唑啉（0.3 - 1 μM）收缩的离体大鼠肠系膜床的影响。1-EBIO（0.1 - 30 nmol）以剂量和内皮依赖性方式降低动脉灌注压力。输注大电导钾通道阻滞剂青霉震颤素A（100 nM）或小电导钙激活钾通道（SK(Ca)）阻滞剂蜂毒明肽（0.5 μM）会使西拉唑啉介导的张力（毫米汞柱）显著增加：103.3±8.7（对照）对比156.3±14.3（青霉震颤素A）；或93.0±15.8（对照）对比114.0±15.4（蜂毒明肽）。青霉震颤素A减弱了1-EBIO的舒张作用，而蜂毒明肽、树眼镜蛇毒素（50 nM；一种电压门控钾通道拮抗剂）或哇巴因（100 μM；一种钠泵阻滞剂）未能改变反应。随着细胞外[K+]增加，1-EBIO介导的舒张作用显著降低：对30 nmol的舒张作用在4.7 mM K+（正常PSS）时为89.3%±3.2%，而在20 mM和80 mM K+ PSS时分别为59.5%±3.4%和19.0%±3.9%。一氧化氮合酶的选择性抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME；100 μM）和一氧化氮敏感的鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ；10 μM）分别消除了在20或80 mM K+ PSS灌注血管中的1-EBIO舒张作用。我们得出结论：（1）大鼠肠系膜动脉血管中存在大电导钾通道和SK(Ca)通道，并对血管张力有积极贡献；（2）1-EBIO的血管舒张作用涉及内皮大电导钾通道的开放和一氧化氮的合成。
