Role of ATP-sensitive potassium channels in brain stem circulation during hypotension.
The basilar artery and its branch arterioles dilate actively in response to a marked decrease in blood pressure and maintain cerebral blood flow (CBF) to the brain stem. We tested the hypothesis that ATP-sensitive potassium (KATP) channels play a role in the autoregulatory responses of the brain stem circulation in vivo. In anesthetized Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and branch arterioles were measured through a cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-6) and 10(-5) mol/l of glibenclamide, a selective KATP-channel blocker, the lower limit of CBF autoregulation shifted upward to 60-75 from 30-45 mmHg in the vehicle group. Glibenclamide significantly impaired the dilator response of small arterioles (baseline diameter 45 +/- 2 microns) throughout hypotension (P < 0.03) but did not impair the dilatation of the basilar artery (247 +/- 3 microns) or large arterioles (99 +/- 4 microns). Thus KATP channels appear to play an important role in the regulation of CBF to the the brain stem during hypotension by mediating the compensatory dilatation of small arterioles. In contrast, these channels may not be a major regulator of the vascular tone of larger arteries during hypotension.
Toyoda
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Fujii
K
K
Ibayashi
S
S
Kitazono
T
T
Nagao
T
T
Fujishima
M
M
D018528:ATP-Binding Cassette Transporters; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001578:Benzopyrans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000098:blood supply*; D002245:Carbon Dioxide / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006706:Homeostasis; D007022:Hypotension / Q000097:blood / Q000503:physiopathology*; D054086:KATP Channels; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D000959:Antihypertensive Agents; D001578:Benzopyrans; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011758:Pyrroles; C092520:uK-ATP-1 potassium channel; D019806:Cromakalim; D002245:Carbon Dioxide; D000109:Acetylcholine; D010100:Oxygen; D005905:Glyburide