Role of endothelial nitric oxide and smooth muscle potassium channels in cerebral arteriolar dilation in response to acidosis.
OBJECTIVE
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 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.


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.
Horiuchi
Tetsuyoshi
T
Department of Neurosurgery, Washington University School of Medicine, St Louis, Mo 63110, USA.
Dietrich
Hans H
HH
Hongo
Kazuhiro
K
Goto
Tetsuya
T
Dacey
Ralph G
RG
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004618:Embolism, Air / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; C121756:N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011188:Potassium; D005905:Glyburide