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(Stroke. 2002;33:844.)
© 2002 American Heart Association, Inc.

Original Contributions

Role of Endothelial Nitric Oxide and Smooth Muscle Potassium Channels in Cerebral Arteriolar Dilation in Response to Acidosis

Tetsuyoshi Horiuchi, MD; Hans H. Dietrich, PhD; Kazuhiro Hongo, MD; Tetsuya Goto, MD Ralph G. Dacey, Jr, MD

From the Department of Neurosurgery, Washington University School of Medicine, St Louis, Mo (T.H., H.H.D., R.G.D.), and Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan (K.H., T.G.).

Correspondence to Hans H. Dietrich, PhD, Department of Neurosurgery, Washington University School of Medicine, Box 8057, 660 S Euclid Ave, St Louis, MO 63110. E-mail DietrichH{at}nsurg.wustl.edu

Background and Purpose— 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.

Methods— 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.

Results— The dilation was significantly inhibited by potassium chloride (30 mmol/L) and glibenclamide (3 µmol/L; ATP-sensitive potassium channel inhibitor). We found that 30 µmol/L BaCl₂ (concentration-dependent potassium channel inhibitor) also affected the dilation; however, an additional treatment of 3 µmol/L glibenclamide did not produce further inhibition. Tetraethylammonium ion (1 mmol/L; calcium-activated potassium channel inhibitor) and 4-aminopyridine (100 µmol/L; voltage-dependent potassium channel inhibitor) as well as ouabain (10 µmol/L; Na-K ATPase inhibitor) and N-methylsulphonyl-6-(2-proparglyloxyphenyl) hexanamide (1 µmol/L; cytochrome P450 epoxygenase inhibitor) did not alter acidotic dilation. N-Monomethyl-L-arginine (10 µmol/L) and N-nitro-L-arginine (10 µmol/L) as nitric oxide synthase inhibitor blunted the dilation. Furthermore, the dilation was significantly attenuated after the endothelial impairment. Additional treatment with glibenclamide (3 µmol/L) further reduced the dilation in response to acidosis.

Conclusions— 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.

Key Words: acid-base equilibrium • cerebral circulation • hydrogen-ion concentration • microcirculation • rats

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