Role of endothelium and arterial K+ channels in mediating hypoxic dilation of middle cerebral arteries.
Isolated middle cerebral arteries of rats were perfused and superfused simultaneously with physiological salt solution (PSS) equilibrated with control (21% O2) or with reduced O2 concentrations (15, 10, 5, or 0% O2). Arterial dilation in response to reduced PO2 was unaffected by the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10 microM) but was inhibited by selective perfusion of the lumen with 21% O2 PSS (0% O2 in the superfusion), endothelial removal, and 1 microM indomethacin. Arterial dilation during reduced PO2 was unaffected by 1 mM tetraethylammonium to block the Ca(2+)-dependent "maxi-K+" channel but was eliminated by 1 microM glibenclamide, a blocker of the ATP-sensitive K+ channel. Glibenclamide also inhibited dilation of the vessels in response to the stable prostacyclin analogue, iloprost. The results of this study suggest that dilation of rat middle cerebral arteries in response to reduced PO2 is mediated by an endothelium-dependent cyclooxygenase product, which activates glibenclamide-sensitive K+ channels.
Fredricks
K T
KT
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Liu
Y
Y
Rusch
N J
NJ
Lombard
J H
JH
D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D010100:Oxygen; D005905:Glyburide