NITRIC-OXIDE MODULATES THE CBF RESPONSE TO INCREASED EXTRACELLULAR POTASSIUM

The response of the regional cerebral blood flow (rCBF) to brain topic al superfusion of 20 mM K+ was characterized in a closed cranial windo w preparation in barbiturate anesthetized and ventilated rats: Increas ing K+ in the artificial cerebrospinal fluid (ACSF) induced a rCBF ele vation (measured by laser-Doppler flowmetry) of +85 +/- 37% above base line (n = 19). This elevation was stable for >3 h with continuous supe rfusion of increased K+ (n = 5) and partially reversible to a level of +18 +/- 19% above baseline when returning to a physiological K+ conce ntration. Nitric oxide synthase (NOS) inhibition by brain topical supe rfusion 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 less than or equal to, 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 dur ing NOS inhibition to restore basal tissue NO levels, the resultant le vel of rCBF was +28 +/- 54% above baseline. Subsequent increase of Kin the presence of NOS inhibition and SNAP elevated rCBF to +137 +/- 8 9% above baseline (n = 4), Statistical analysis comparing K+-induced e levation of rCBF (a) without any added drugs, (b) in the presence of N OS inhibition with L-NA, and (c) in the presence of both NOS inhibitio n and SNAP revealed that K+-induced elevation in the presence of NOS i nhibition was significantly reduced (p less than or equal to 0.05) whe reas no statistical difference was found between K+ induced elevation of rCBF without drugs compared with the K+-induced elevation of rCBF i n the presence of L-NA and SNAP, We conclude that NO is a modulator of the rCBF elevation to increased extracellular K+ concentration.