Onoue H, Katusic Z S
Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Stroke. 1997 Jun;28(6):1264-70; discussion 1270-1. doi: 10.1161/01.str.28.6.1264.
The mechanisms underlying smooth muscle relaxations of cerebral arteries in response to nitric oxide (NO) and cyclic GMP (cGMP) are still not completely understood. The present study was designed to determine the role of potassium channels in the relaxations to NO donors 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP), as well as 8-bromo-3',5' -cGMP (a synthetic analogue of cGMP) and zaprinast (a selective cGMP phosphodiesterase inhibitor).
Rings of canine middle cerebral asteries without endothelium were suspended in Krebs-Ringer bicarbonate solution for isometric tension recording. The levels of cGMP were measured by radioimmunoassay. Relaxations to NO donors 8-bromo-cGMP and zaprinast were studied in the presence and in the absence of K+ channel blockers charybdotoxin (large-conductance Ca(2+)-activated K+ channels), glyburide (ATP-sensitive K+ channels), 4-aminopyridine (delayed rectifier K+ channels), and BaCl2 (multiple types of K+ channels).
Concentration-dependent relaxations caused by NO donors (SIN-1 and SNP) were significantly reduced in arteries treated with BaCl2 (3 x 10(-4) mol/L) or charybdotoxin (3 x 10(-8) mol/L). Relaxations to 8-bromo-cGMP were not affected by the same concentrations of BaCl2 and charybdotoxin; however, they were reduced by higher concentrations of BaCl2 (3 x 10(-3) mol/L) or charybdotoxin (10(-7) mol/L). Zaprinast-induced relaxations were significantly reduced by BaCl2 (3 x 10(-4) mol/L) or charybdotoxin (3 x 10(-8) mol/L). Glyburide (10(-5) mol/L) and 4-aminopyridine (10(-3) mol/L) did not alter the relaxations to SIN-1 or SNP. The production of cGMP stimulated by SIN-1 in the vascular smooth muscle was not affected by BaCl2 (3 x 10(-3) mol/L) or charybdotoxin (10(-7) mol/L).
These results indicate that in canine middle cerebral arteries, a significant portion of relaxations to NO liberated from nitrovasodilators is mediated by large-conductance Ca(2+)-activated K+ channels. Other K+ channels, sensitive to BaCl2, may also be involved in the mechanism of relaxations induced by NO.
脑动脉平滑肌对一氧化氮（NO）和环磷酸鸟苷（cGMP）产生舒张反应的潜在机制仍未完全明确。本研究旨在确定钾通道在对NO供体3-吗啉代辛二酰亚胺（SIN-1）和硝普钠（SNP），以及8-溴-3',5'-环磷酸鸟苷（cGMP的一种合成类似物）和扎普司特（一种选择性cGMP磷酸二酯酶抑制剂）产生舒张反应中的作用。
将无内皮的犬大脑中动脉环悬挂于 Krebs-Ringer 碳酸氢盐溶液中进行等长张力记录。采用放射免疫分析法测定 cGMP 水平。在存在和不存在钾通道阻滞剂（蝎毒素（大电导钙激活钾通道））、格列本脲（ATP 敏感性钾通道）、4-氨基吡啶（延迟整流钾通道）和 BaCl₂（多种类型钾通道）的情况下，研究对 NO 供体 8-溴-cGMP 和扎普司特的舒张反应。
在用 BaCl₂（3×10⁻⁴mol/L）或蝎毒素（3×10⁻⁸mol/L）处理的动脉中，由 NO 供体（SIN-1 和 SNP）引起的浓度依赖性舒张反应显著降低。对 8-溴-cGMP 的舒张反应不受相同浓度的 BaCl₂和蝎毒素影响；然而，它们会被更高浓度的 BaCl₂（3×10⁻³mol/L）或蝎毒素（10⁻⁷mol/L）降低。扎普司特诱导的舒张反应被 BaCl₂（3×10⁻⁴mol/L）或蝎毒素（3×10⁻⁸mol/L）显著降低。格列本脲（10⁻⁵mol/L）和 4-氨基吡啶（10⁻³mol/L）未改变对 SIN-1 或 SNP 的舒张反应。SIN-1 在血管平滑肌中刺激产生的 cGMP 不受 BaCl₂（3×10⁻³mol/L）或蝎毒素（10⁻⁷mol/L）影响。
这些结果表明，在犬大脑中动脉中，从硝基血管扩张剂释放的 NO 所引起的舒张反应的很大一部分是由大电导钙激活钾通道介导的。对 BaCl₂敏感的其他钾通道也可能参与 NO 诱导的舒张机制。
