Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis.
We tested the hypothesis that the CBF response to extracellular acidosis is mediated by nitric oxide (NO). A closed cranial window, superfused with artificial CSF (aCSF), was implanted over the parietal cortex in anesthetized and ventilated Wistar rats. Regional cerebral blood flow (rCBF) was measured continuously with laser-Doppler flowmetry (LDF). The reaction of rCBF to hypercapnia (PaCO2 from 30.5 +/- 1.8 to 61.3 +/- 5.8 mm Hg by adding CO2 to the inspiratory gas) was 2.9 +/- 1.4%/mm Hg, and the reaction of rCBF to H+ (superfusion of acidic aCSF, pH 7.07 +/- 0.05) was 101.7 +/- 24.7%/pH unit. The regional NO synthase (NOS) activity was blocked by superfusing aCSF containing 10(-3) M N omega-nitro-L-arginine (L-NA, n = 10). After 30 min of L-NA superfusion, rCBF was reduced to 80.1 +/- 6.5% of baseline, and the rCBF responses to hypercapnia (PaCO2 from 30.9 +/- 2.9 to 58.8 +/- 7.7 mm Hg) and extracellular acidosis (aCSF pH 7.08 +/- 0.06) were reduced to 0.8 +/- 1.1%/mm Hg and 10.1 +/- 23.0%/pH unit, respectively (both p < 0.001). This effect was stereospecific since aCSF containing 10(-3) M N omega-nitro-D-arginine affected neither baseline rCBF nor the response to H+ (n = 5). The NOS blockade did not affect the vasodilatation by the NO donor sodium nitroprusside (n = 5, 114.3 +/- 25.1% before vs. 130.2 +/- 24.7% after NOS blockade). The results confirm the involvement of NO in the CBF reaction to hypercapnia and demonstrate for the first time that NOS blockade also strongly attenuates the H+ response of the cerebral vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
Niwa
K
K
Department of Neurology, University of Munich, Germany.
Lindauer
U
U
Villringer
A
A
Dirnagl
U
U
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine