Santa Naohiko, Kitazono Takanari, Ago Tetsuro, Ooboshi Hiroaki, Kamouchi Masahiro, Wakisaka Masanori, Ibayashi Setsuro, Iida Mitsuo
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Stroke. 2003 May;34(5):1276-80. doi: 10.1161/01.STR.0000068171.01248.97. Epub 2003 Apr 3.
During cerebral ischemia, both hypoxia and hypercapnia appear to produce marked dilatation of the cerebral arteries. Hypercapnia and hypoxia may be accompanied by extracellular and intracellular acidosis, which is another potent dilator of cerebral arteries. However, the precise mechanism by which acidosis produces dilatation of the cerebral arteries is not fully understood. The objective of the present study was to examine the mechanisms by which intracellular acidosis produces dilatation of the basilar artery in vivo.
Using a cranial window in anesthetized rats, we examined responses of the basilar artery to sodium propionate, which was used to cause intracellular acidosis specifically. Expression of subunits of potassium channels was determined by reverse transcription and polymerase chain reaction (RT-PCR).
Topical application of propionate increased diameter of the basilar artery in a concentration-related manner. Propionate-induced dilatation of the artery was attenuated by glibenclamide, an inhibitor of ATP-sensitive potassium channels. However, inhibitors of nitric oxide synthase (N(G)-nitro-L-arginine), large-conductance calcium-activated potassium channels (iberiotoxin), and cyclooxygenase (indomethacin) did not affect the vasodilatation. Expression of mRNA for SUR2B and Kir6.1 was detected, with the use of RT-PCR, in the cultured basilar arterial muscle cells.
The findings suggest that intracellular acidification may produce dilatation of the basilar artery through activation of ATP-sensitive potassium channels in vivo. Kir6.1/SUR2B may be the major potassium channels that mediate propionate-induced dilatation of the artery.
在脑缺血期间，缺氧和高碳酸血症似乎都会使脑动脉显著扩张。高碳酸血症和缺氧可能伴有细胞外及细胞内酸中毒，而酸中毒是脑动脉的另一种强效扩张剂。然而，酸中毒导致脑动脉扩张的确切机制尚未完全明确。本研究的目的是探讨细胞内酸中毒在体内引起基底动脉扩张的机制。
在麻醉大鼠中使用颅骨开窗技术，我们检测了基底动脉对丙酸钠的反应，丙酸钠专门用于引发细胞内酸中毒。通过逆转录聚合酶链反应（RT-PCR）测定钾通道亚基的表达。
局部应用丙酸钠以浓度相关的方式增加了基底动脉的直径。丙酸钠诱导的动脉扩张被格列本脲（一种ATP敏感性钾通道抑制剂）减弱。然而，一氧化氮合酶抑制剂（N(G)-硝基-L-精氨酸）、大电导钙激活钾通道抑制剂（iberiotoxin）和环氧化酶抑制剂（吲哚美辛）均不影响血管舒张。使用RT-PCR在培养的基底动脉肌细胞中检测到了SUR2B和Kir6.1的mRNA表达。
这些发现表明，细胞内酸化可能通过在体内激活ATP敏感性钾通道而导致基底动脉扩张。Kir6.1/SUR2B可能是介导丙酸钠诱导动脉扩张的主要钾通道。
