Nitric oxide appears to mediate the immune functions of macrophages, t
he influence of endothelial cells on blood vessel relaxation, and also
to serve as a neurotransmitter in the central and peripheral nervous
system.(1,17) Macrophage nitric oxide synthase is inducible with massi
ve increases in new nitric oxide synthase protein synthesis following
immune stimulation of macrophages.(18) By contrast, endothelial nitric
oxide synthase and neuronal nitric oxide synthase are thought to tie
constitutive with activation induced by calcium entry into cells in th
e absence of new protein synthesis.(4,9,15) Developmental studies show
ing the transient expression of neuronal nitric oxide synthase in embr
yonic and early postnatal life in rodent spinal motoneurons and cerebr
al cortical plate neurons (Bredt and Snyder, unpublished observations)
implies inducibility of neuronal nitric oxide synthase. Moreover, neu
ronal nitric oxide synthase expression is greatly enhanced in sensory
ganglia following peripheral axotomy.(8,20) Staining for NADPH diaphor
ase in spinal motoneurons is greatly increased following ventral root
avulsion.(22) In many parts of the Central Nervous System NADPH diapho
rase staining reflects nitric oxide synthase.(3,11) In the present stu
dy, we have combined in situ hybridization for neuronal nitric oxide s
ynthase, immunohistochemical staining of neuronal nitric oxide synthas
e, and NADPH diaphorase staining to establish that neuronal nitric oxi
de synthase expression is markedly augmented in spinal motoneurons fol
lowing avulsion. The generality of this effect is evident from augment
ed staining in nucleus dorsalis following spinal cord transection.