Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression.
The role of nitric oxide (NO) in cerebral blood flow-metabolism coupling was assessed in SV-129 wild-type (WT) and neuronal (type I) NO synthase (NOS) knockout mice (Kn). Regional cerebral blood flow (rCBF; laser-Doppler flowmetry) was measured over the contralateral cortical barrel field during unilateral mechanical vibrissal deflection (2-3 Hz, 60 s) under urethan anesthesia. The rCBF response was similar in WT and Kn and did not differ when recorded over the intact skull or closed cranial window preparations. Whisker stimulation increased rCBF by 41 +/- 8% (maximum) and 27 +/- 6% (mean) in WT (n = 6) and 41 +/- 7% (maximum) and 26 +/- 6% (mean) in Kn (n = 6) when recorded through a closed cranial window. After superfusion with topical N omega-nitro-L-arginine (L-NNA; 1 mM), the rCBF response was inhibited by approximately 45% in WT mice (P < 0.05), whereas there was no inhibition in Kn. Endothelium-dependent relaxation, assessed by pial vessel dilation in response to topical acetylcholine (100 microM) and inhibition by L-NNA (1 mM), was the same in both groups. Our results suggest that 1) endothelial NO production does not mediate the rCBF coupling to neuronal activity in Kn, 2) the inhibitory effect of L-NNA on the rCBF response to whisker stimulation in WT is a consequence of type I (neuronal) NOS inhibition, and 3) NO-independent mechanisms couple rCBF and metabolism during whisker stimulation in mice lacking expression of neuronal NOS.
Ma
J
J
Neurosurgical Services and Neurology Department, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Ayata
C
C
Huang
P L
PL
Fishman
M C
MC
Moskowitz
M A
MA
D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology*
D019001:Nitric Oxide Synthase