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% O-2) or with reduced O-2 concentrations (15, 10, 5, or O% O-2). Arterial dilation in response to reduced Po, was unaffected by the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10 mu M) but was inhibited by selective perfusion of the lumen with 21% Oz PSS (0% O-2 in the superfusion), endothelial removal, and 1 mu M indomethacin. Arterial dilation during reduced Pot was unaffected by 1 mM tetraethylammonium to block the Ca2+- dependent ''maxi-K''' channel but was eliminated by 1 mu M 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.