Mechanisms of cerebral arterial relaxations to hydrogen peroxide

Background and Purpose-The role of hydrogen peroxide in the regulation of c erebral arterial tone is not completely understood. Previous studies have d emonstrated that hydrogen peroxide causes vasodilation of small cerebral ar teries. The present study was designed to determine the mechanisms responsi ble for relaxations of large cerebral arteries to hydrogen peroxide, Methods-Rings of canine middle cerebral arteries without endothelium were s uspended for isometric force recording in modified Krebs-Ringer bicarbonate solution bubbled with 94% O-2/6% CO2 (37 degrees C, pH 7.4), Radioimmunoas say technique was used to determine the levels of cAMP and cGMP, Results-During contraction to UTP (3x10(-6) or 10(-5) mol/L), hydrogen pero xide (10(-6) to 10(-4) mol/L) caused concentration-dependent relaxations. C atalase (1200 U/mL) abolished the relaxations to hydrogen peroxide, Inhibit ion of cyclooxygenase by indomethacin (10-5 mol/L) significantly reduced re laxations to hydrogen peroxide. In arteries contracted by KCl (20 mmol/L), the relaxations to hydrogen peroxide were significantly reduced. In the pre sence of a nonselective potassium channel inhibitor, BaCl2 (10-4 mol/L), a delayed rectifier potassium channel inhibitor, 4-aminopyridine (10(-3) mol/ L), or a calcium-activated potassium channel inhibitor, charybdotoxin (3X10 (-8) mol/L), the relaxations to hydrogen peroxide were also significantly r educed. An ATP-sensitive potassium channel inhibitor, glyburide (5X10(-6) m ol/L), did not affect the relaxations to hydrogen peroxide. Hydrogen peroxi de produced concentration-dependent increase in levels of cAMP. Indomethaci n (10-5 mol/L) inhibited the stimulatory effect of hydrogen peroxide on cAM P production. In contrast, hydrogen peroxide did not affect the levels of c GMP. Conclusions-These results suggest that hydrogen peroxide may cause relaxati ons of large cerebral arteries in part by activation of arachidonic acid me tabolism via cyclooxygenase pathway with subsequent increase in cAMP levels and activation of potassium channels.