Sun C W, Falck J R, Okamoto H, Harder D R, Roman R J
Department of Physiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Am J Physiol Heart Circ Physiol. 2000 Jul;279(1):H339-50. doi: 10.1152/ajpheart.2000.279.1.H339.
This study examined the response to nitric oxide (NO) in rat middle cerebral arteries (MCA). NO donors increased the activity of a 205-pS K(+) channel recorded from vascular smooth muscle (VSM) cells isolated from MCA 10-fold. Blockade of guanylyl cyclase activity with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10(-5) M) did not alter the effect of NO on this channel. In contrast, adding 20-hydroxyeicosatetraenoic acid (20-HETE) to the bath (10(-7) M) abolished the response to NO. NO donors also increased the diameter of serotonin-preconstricted MCA to 85% of control. Blockade of K(+) channels with iberiotoxin or a high-K(+) medium reduced this response by 50%. ODQ (10(-5) M) reduced this response by 47 +/- 3%, whereas preventing the fall of 20-HETE levels reduced the response by 59 +/- 2% (n = 5). Blockade of both pathways eliminated the response to NO donors. These results indicate that activation of K(+) channels contributes 50% to vasodilator response to NO in rat MCA. This is mediated by a fall in 20-HETE levels rather than a rise in cGMP levels or a direct effect of NO.
本研究检测了大鼠大脑中动脉（MCA）对一氧化氮（NO）的反应。NO供体使从MCA分离的血管平滑肌（VSM）细胞中记录到的205-pS钾通道活性增加了10倍。用1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮（ODQ，10⁻⁵ M）阻断鸟苷酸环化酶活性并未改变NO对该通道的作用。相反，向浴槽中加入20-羟基二十碳四烯酸（20-HETE，10⁻⁷ M）可消除对NO的反应。NO供体还使5-羟色胺预收缩的MCA直径增加至对照的85%。用iberiotoxin或高钾培养基阻断钾通道可使该反应降低50%。ODQ（10⁻⁵ M）使该反应降低47±3%，而阻止20-HETE水平下降可使反应降低59±2%（n = 5）。同时阻断这两条途径可消除对NO供体的反应。这些结果表明，钾通道的激活对大鼠MCA中NO介导的血管舒张反应的贡献为50%。这是由20-HETE水平下降介导的，而非cGMP水平升高或NO的直接作用。
