ATP-sensitive potassium channels mediate dilatation of basilar artery in response to intracellular acidification in vivo.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Santa
Naohiko
N
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kitazono
Takanari
T
Ago
Tetsuro
T
Ooboshi
Hiroaki
H
Kamouchi
Masahiro
M
Wakisaka
Masanori
M
Ibayashi
Setsuro
S
Iida
Mitsuo
M
D018528:ATP-Binding Cassette Transporters; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007424:Intracellular Fluid / Q000737:chemistry; D017136:Ion Transport / Q000187:drug effects*; D046911:Macromolecular Substances; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009928:Organ Specificity; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D064233:Sulfonylurea Receptors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D020030:Nitric Oxide Donors; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D011422:Propionates; D011955:Receptors, Drug; D017923:Sodium-Hydrogen Exchangers; D064233:Sulfonylurea Receptors; C057360:5-(N,N-hexamethylene)amiloride; D009599:Nitroprusside; D019335:Nitroarginine; C064719:iberiotoxin; D000584:Amiloride; C514135:sodium propionate; D019001:Nitric Oxide Synthase; C029658:propionic acid; D011188:Potassium; D005905:Glyburide; D007213:Indomethacin