Horiuchi Tetsuyoshi, Dietrich Hans H, Hongo Kazuhiro, Goto Tetsuya, Dacey Ralph G
Department of Neurosurgery, Washington University School of Medicine, St Louis, Mo 63110, USA.
Stroke. 2002 Mar;33(3):844-9. doi: 10.1161/hs0302.104112.
Potassium channels or nitric oxide or both are major mediators of acidosis-induced dilation in the cerebral circulation. However, these contributions depend on a variety of factors such as species and vessel location. The present study was designed to clarify whether potassium channels and endothelial nitric oxide are involved in acidosis-induced dilation of isolated rat cerebral arterioles.
Cerebral arterioles were cannulated and monitored with an inverted microscope. Acidosis (pH 6.8 to 7.4) produced by adding hydrogen ions mediated dilation of the cerebral arterioles in a concentration-dependent manner. The role of nitric oxide and potassium channels in response to acidosis was examined with several specific inhibitors and endothelial damage.
The dilation was significantly inhibited by potassium chloride (30 mmol/L) and glibenclamide (3 micromol/L; ATP-sensitive potassium channel inhibitor). We found that 30 micromol/L BaCl2 (concentration-dependent potassium channel inhibitor) also affected the dilation; however, an additional treatment of 3 micromol/L glibenclamide did not produce further inhibition. Tetraethylammonium ion (1 mmol/L; calcium-activated potassium channel inhibitor) and 4-aminopyridine (100 micromol/L; voltage-dependent potassium channel inhibitor) as well as ouabain (10 micromol/L; Na-K ATPase inhibitor) and N-methylsulphonyl-6-(2-proparglyloxyphenyl) hexanamide (1 micromol/L; cytochrome P450 epoxygenase inhibitor) did not alter acidotic dilation. N(omega)-Monomethyl-L-arginine (10 micromol/L) and N(omega)-nitro-L-arginine (10 micromol/L) as nitric oxide synthase inhibitor blunted the dilation. Furthermore, the dilation was significantly attenuated after the endothelial impairment. Additional treatment with glibenclamide (3 micromol/L) further reduced the dilation in response to acidosis.
Endothelial nitric oxide and smooth muscle ATP-sensitive potassium channels contribute to acidosis-induced dilation of rat cerebral arterioles. Endothelial damage caused by pathological conditions such as subarachnoid hemorrhage or traumatic brain injury may contribute to reduced blood flow despite injury-induced cerebral acidosis.
钾通道或一氧化氮或两者都是酸中毒诱导脑循环扩张的主要介质。然而，这些作用取决于多种因素，如物种和血管位置。本研究旨在阐明钾通道和内皮一氧化氮是否参与酸中毒诱导的离体大鼠脑动脉扩张。
将脑动脉插管并通过倒置显微镜进行监测。通过添加氢离子产生的酸中毒（pH 6.8至7.4）以浓度依赖的方式介导脑动脉扩张。用几种特异性抑制剂和内皮损伤来研究一氧化氮和钾通道对酸中毒的反应。
氯化钾（30 mmol/L）和格列本脲（3 μmol/L；ATP敏感性钾通道抑制剂）显著抑制扩张。我们发现30 μmol/L氯化钡（浓度依赖性钾通道抑制剂）也影响扩张；然而，额外给予3 μmol/L格列本脲并未产生进一步抑制作用。四乙铵离子（1 mmol/L；钙激活钾通道抑制剂）和4-氨基吡啶（100 μmol/L；电压依赖性钾通道抑制剂）以及哇巴因（10 μmol/L；钠钾ATP酶抑制剂）和N-甲基磺酰基-6-（2-炔丙氧基苯基）己酰胺（1 μmol/L；细胞色素P450环氧合酶抑制剂）并未改变酸中毒诱导的扩张。一氧化氮合酶抑制剂N（ω）-单甲基-L-精氨酸（10 μmol/L）和N（ω）-硝基-L-精氨酸（10 μmol/L）减弱了扩张。此外，内皮损伤后扩张显著减弱。额外给予格列本脲（3 μmol/L）进一步降低了对酸中毒的扩张反应。
内皮一氧化氮和平滑肌ATP敏感性钾通道参与酸中毒诱导的大鼠脑动脉扩张。蛛网膜下腔出血或创伤性脑损伤等病理状况引起的内皮损伤可能导致尽管有损伤诱导的脑酸中毒但血流量仍减少。
