Takaba H, Nagao T, Ibayashi S, Kitazono T, Fujii K, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hypertension. 1996 Jul;28(1):143-6. doi: 10.1161/01.hyp.28.1.143.
We examined whether the effect of Y-26763, an ATP-sensitive potassium channel opener, on cerebral blood flow is altered in stroke-prone spontaneously hypertensive rats (SHRSP) and, if altered, whether long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor, is capable of preventing the change. Cerebral blood flow during intracarotid infusion of Y-26763 was measured in anesthetized SHRSP and normotensive Wistar-Kyoto rats (WKY) as control. Y-26763 increased cerebral blood flow in a dose-dependent manner in WKY, and glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, inhibited the Y-26763-induced increase in cerebral blood flow. In contrast, the response to Y-26763 in SHRSP was significantly impaired compared with that in WKY. Antihypertensive treatment with cilazapril lowered blood pressure toward normal and prevented the impaired response in cerebral blood flow to Y-26763 in SHRSP. These findings suggest that (1) ATP-sensitive potassium channels contribute to the regulation of cerebral blood flow in rats, (2) the response to an ATP-sensitive potassium channel opener is markedly diminished in hypertensive rats, and (3) the altered response to an ATP-sensitive potassium channel opener during chronic hypertension can be prevented by long-term antihypertensive treatment.
我们研究了ATP敏感性钾通道开放剂Y-26763对易卒中型自发性高血压大鼠（SHRSP）脑血流量的影响是否发生改变，以及如果发生改变，血管紧张素转换酶抑制剂西拉普利的长期降压治疗是否能够预防这种改变。在麻醉的SHRSP和作为对照的正常血压Wistar-Kyoto大鼠（WKY）中测量颈内动脉输注Y-26763期间的脑血流量。Y-26763在WKY中以剂量依赖性方式增加脑血流量，而ATP敏感性钾通道的选择性抑制剂格列本脲抑制Y-26763诱导的脑血流量增加。相比之下，与WKY相比，SHRSP对Y-26763的反应明显受损。用西拉普利进行的降压治疗使血压降至正常，并预防了SHRSP中脑血流量对Y-26763的受损反应。这些发现表明：（1）ATP敏感性钾通道有助于调节大鼠的脑血流量；（2）高血压大鼠对ATP敏感性钾通道开放剂的反应明显减弱；（3）长期降压治疗可以预防慢性高血压期间对ATP敏感性钾通道开放剂的反应改变。
