L-NNA decreases cortical hyperemia and brain cGMP levels following CO2 inhalation in Sprague-Dawley rats.
The role of nitric oxide (NO) in the response to 5% CO2 inhalation was investigated by measuring 1) regional cerebral blood flow (rCBF) by laser-Doppler flowmetry and pial vessel diameter through a closed cranial window after topical NG-nitro-L-arginine (L-NNA, 1 mM), and 2) the time-dependent changes in brain guanosine 3',5'-cyclic monophosphate (cGMP) levels after L-NNA (10 mg/kg ip). When L-NNA (but not NG-nitro-D-arginine) was applied topically for 30 or 60 min, the response to hypercapnia was significantly attenuated. A correlation was found between inhibition of brain NO synthase (NOS) activity and the rCBF response (r = 0.77; P < 0.01). However, L-NNA applied 15 min before hypercapnia did not attenuate the increase in rCBF but did attenuate the dilation to topical acetylcholine. Inhalation of CO2 (5%) elevated brain cGMP levels by 20-25%, and L-NNA reduced this response. These data from the rat suggest that 1) a product of NOS activity is associated with hypercapnic hyperemia and the attendant increase in brain cGMP levels, and 2) hypercapnic blood flow changes may not be dependent on endothelial NOS activity within pial vessels.
Irikura
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K
Stroke Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Maynard
K I
KI
Lee
W S
WS
Moskowitz
M A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000287:Administration, Topical; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D006935:Hypercapnia / Q000503:physiopathology; D006940:Hyperemia / Q000503:physiopathology*; D008297:Male; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D002245:Carbon Dioxide; D019335:Nitroarginine; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine