Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Acta Pharmacol Sin. 2011 Feb;32(2):194-200. doi: 10.1038/aps.2010.195.
To investigate the role of ATP-sensitive potassium (K(ATP)) channels on blood pressure variability (BPV) in sinoaortic denervated (SAD) rats.
SAD was performed on male Sprague-Dawley rats 4 weeks before the study. mRNA expression of Kir6.1, Kir6.2 and SUR2 in aorta and mesenteric artery was determined using real-time quantitative polymerase chain reaction, and confirmed at the protein level using Western blotting and laser confocal immunofluorescence assays. Concentration-response curves of isolated aortic and mesenteric arterial rings to adenosine and pinacidil were established. Effects of K(ATP) channel openers and blocker on BPV were examined in conscious SAD rats.
Aortic SUR2 expression was significantly greater, while Kir6.1 was lower, in SAD rats than in sham-operated controls. In contrast, in the mesenteric artery both SUR2 and Kir6.1 expression were markedly lower in SAD rats than controls. For both arteries, Kir6.2 expression was indistinguishable between sham-operated and SAD rats. These findings were confirmed at the protein level. Responses of the aorta to both adenosine and pinacidil were enhanced after SAD, while the mesenteric response to adenosine was attenuated. Pinacidil, diazoxide, nicorandil, and glibenclamide significantly decreased BPV.
These findings indicate that expression of vascular K(ATP) channels is altered by chronic SAD. These alterations influence vascular reactivity, and may play a role in the increased BPV in chronic SAD rats.
探讨三磷酸腺苷敏感性钾（K(ATP)）通道在去窦弓神经（SAD）大鼠血压变异性（BPV）中的作用。
SAD 在研究前 4 周对雄性 Sprague-Dawley 大鼠进行。使用实时定量聚合酶链反应测定主动脉和肠系膜动脉中 Kir6.1、Kir6.2 和 SUR2 的 mRNA 表达，并使用 Western 印迹和激光共聚焦免疫荧光测定法在蛋白质水平上进行确认。建立分离的主动脉和肠系膜动脉环对腺苷和匹那地尔的浓度-反应曲线。在清醒的 SAD 大鼠中检查 K(ATP)通道开放剂和阻滞剂对 BPV 的影响。
与假手术对照组相比，SAD 大鼠主动脉 SUR2 表达明显增加，而 Kir6.1 表达降低。相比之下，SAD 大鼠肠系膜动脉中 SUR2 和 Kir6.1 的表达明显低于对照组。对于这两种动脉，Sham 手术和 SAD 大鼠之间的 Kir6.2 表达没有区别。这些发现得到了蛋白质水平的证实。SAD 后，主动脉对腺苷和匹那地尔的反应增强，而肠系膜对腺苷的反应减弱。匹那地尔、二氮嗪、尼克地尔和格列本脲显著降低了 BPV。
这些发现表明，慢性 SAD 改变了血管 K(ATP) 通道的表达。这些改变影响血管反应性，并可能在慢性 SAD 大鼠中增加 BPV 中起作用。
