Potassium channels mediate dilatation of cerebral arterioles in response to arachidonate

被引:56
作者
Sobey, CG
Heistad, DD
Faraci, FM
机构
[1] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Coll Med, Ctr Cardiovasc, Dept Pharmacol, Iowa City, IA 52242 USA
[3] Univ Melbourne, Dept Pharmacol, Parkville, Vic 3052, Australia
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1998年 / 275卷 / 05期
关键词
hydrogen peroxide; calcium-activated potassium channels; reactive oxygen species; iberiotoxin; cyclooxygenase;
D O I
10.1152/ajpheart.1998.275.5.H1606
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We tested the hypothesis that cerebral vasodilatation in response to arachidonate is dependent on activation of cyclooxygenase and cytochrome P-450 pathways and formation of endogenous reactive oxygen species and is mediated by activation of potassium channels. The diameter of cerebral arterioles was measured using cranial windows in anesthetized rats. Under control conditions [baseline diameter = 45 +/- mu m (mean +/- SE)], arachidonate (1-100 mu M) and papaverine (10-50 mu M) produced concentration-dependent vasodilatation. Cerebral vasodilator responses to arachidonate, but not papaverine, were abolished during topical application of indomethacin (10 mu M, an inhibitor of cyclooxygenase) or catalase (100 U/ml, which inactivates hydrogen peroxide). In contrast, clotrimazole (10 mu M) and 17-ODYA (20 mu M), inhibitors of cytochrome P-450 activity, had no effect on dilator responses of cerebral arterioles to arachidonate. Superoxide dismutase (SOD, 100 U/ml) had no effect on vasodilator responses to papaverine or lower concentrations of arachidonate, whereas dilator responses to 100 mu M arachidonate were inhibited modestly (by 22%) by SOD. similarly deferoxamine (1 mM) partly inhibited dilator responses to 10 and 100 mu M arachidonate (by similar to 30% at each concentration). Tetraethylammonium ion (1 mM) or iberiotoxin (50 nM), inhibitors of calcium-activated potassium channels, markedly inhibited vasodilatation in response to arachidonate (by 70-90%) but not papaverine. These findings suggest that dilatation of cerebral arterioles in response to arachidonate is mediated largely by endogenously formed reactive oxygen species, which are generated from cyclooxygenase activity, and activation of calcium-activated potassium channels. Thus activation of potassium channels appears to be a major mechanism of cerebral vasodilatation in response to reactive oxygen species produced endogenously.
引用
收藏
页码:H1606 / H1612
页数:7
相关论文
共 37 条
[1]  
ALVAREZ J, 1992, J BIOL CHEM, V267, P11789
[2]   POSTISCHEMIC GENERATION OF SUPEROXIDE ANION BY NEWBORN PIG BRAIN [J].
ARMSTEAD, WM ;
MIRRO, R ;
BUSIJA, DW ;
LEFFLER, CW .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (02) :H401-H403
[3]   HYDROGEN-PEROXIDE - AN ENDOGENOUS SMOOTH-MUSCLE CELL HYPERPOLARIZING FACTOR [J].
BENY, JL ;
VONDERWEID, PY .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (01) :378-384
[4]   REGULATION OF ARTERIAL TONE BY ACTIVATION OF CALCIUM-DEPENDENT POTASSIUM CHANNELS [J].
BRAYDEN, JE ;
NELSON, MT .
SCIENCE, 1992, 256 (5056) :532-535
[5]   EFFECTS OF INDOMETHACIN ON CEREBRAL BLOOD-FLOW DURING HYPERCAPNIA IN CATS [J].
BUSIJA, DW ;
HEISTAD, DD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1983, 244 (04) :H519-H524
[6]   Effects of cytochrome P450 inhibitors on potassium currents and mechanical activity in rat portal vein [J].
Edwards, G ;
Zygmunt, PM ;
Hogestatt, ED ;
Weston, AH .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 119 (04) :691-701
[7]   DILATION OF CEREBRAL ARTERIOLES BY CYTOCHROME-P-450 METABOLITES OF ARACHIDONIC-ACID [J].
ELLIS, EF ;
POLICE, RJ ;
YANCEY, L ;
MCKINNEY, JS ;
AMRUTHESH, SC .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (04) :H1171-H1177
[8]  
FARACI FM, IN PRESS J CEREBRAL
[9]   OXYGEN RADICALS IN CEREBRAL VASCULAR INJURY [J].
KONTOS, HA .
CIRCULATION RESEARCH, 1985, 57 (04) :508-516
[10]   OXYGEN RADICALS MEDIATE THE CEREBRAL ARTERIOLAR DILATION FROM ARACHIDONATE AND BRADYKININ IN CATS [J].
KONTOS, HA ;
WEI, EP ;
POVLISHOCK, JT ;
CHRISTMAN, CW .
CIRCULATION RESEARCH, 1984, 55 (03) :295-303