Cerebrovascular alterations in mice lacking neuronal nitric oxide synthase gene expression

Nitric oxide (NO) is known to mediate increases in regional cerebral blood flow elicited by CO₂ inhalation. In mice with deletion of the gene for neuronal NO synthase (NOS), CO₂ inhalation augments cerebral blood flow to the same extent as in wild-type mice. However, unlike wild-type mice, the increased flow in mutants is not blocked by the NOS inhibition, N(ω)-nitro- L-arginine, and CO₂ exposure fails to increase brain levels of cGMP. Topical acetylcholine elicits vasodilation in the mutants which is blocked by N(ω)- nitro-L-arginine, indicating normal functioning of endothelial NOS. Moreover, immunohistochemical staining for endothelial NOS is normal in the mutants. Thus, following loss of neuronal NOS, the cerebral circulatory response is maintained by a compensatory system not involving NO.