Blockade of Nitric Oxide Synthesis in Rats Strongly Attenuates the CBF Response to Extracellular Acidosis

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Abstract
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 Nω-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 Nω-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. We speculate that extracellular acidification triggers the production of NO.