Nitric oxide modulates the CBF response to increased extracellular potassium.
The response of the regional cerebral blood flow (rCBF) to brain topical superfusion of 20 mM K+ was characterized in a closed cranial window preparation in barbiturate anesthetized and ventilated rats: Increasing K+ in the artificial cerebrospinal fluid (ACSF) induced a rCBF elevation (measured by laser-Doppler flowmetry) of +85 +/- 37% above baseline (n = 19). This elevation was stable for > 3 h with continuous superfusion of increased K+ (n = 5) and partially reversible to a level of +18 +/- 19% above baseline when returning to a physiological K+ concentration. Nitric oxide synthase (NOS) inhibition by brain topical superfusion with N omega-nitro-L-arginine (L-NA) revealed (a) Addition of L-NA to high-potassium ACSF reduced the rCBF increase from +94 +/- 36% to +21 +/- 18% (p < or = 0.01, n = 7). (b) When L-NA was superfused for 60 min before increasing K+, rCBF decreased to -17 +/- 7% below baseline. Subsequent coapplication of L-NA and increased K+ induced only an elevation of +7 +/- 4% above baseline (n = 4). (c) When the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was added during NOS inhibition to restore basal tissue NO levels, the resultant level of rCBF was +28 +/- 54% above baseline. Subsequent increase of K+ in the presence of NOS inhibition and SNAP elevated rCBF to +137 +/- 89% above baseline (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
Dreier
J P
JP
Department of Neurology, Charité Humboldt University, Berlin, Germany.
Körner
K
K
Görner
A
A
Lindauer
U
U
Weih
M
M
Villringer
A
A
Dirnagl
U
U
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine
D019335:Nitroarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D010396:Penicillamine; D011188:Potassium