T. Tagawa et al., NITRIC-OXIDE INFLUENCES NEURONAL-ACTIVITY IN THE NUCLEUS-TRACTUS-SOLITARIUS OF RAT BRAIN-STEM SLICES, Circulation research, 75(1), 1994, pp. 70-76
Nitric oxide (NO) is shown to be synthesized in the central nervous sy
stem as well as in vascular endotheliaI cells. However, the physiologi
cal role of NO in cardiovascular regulation in the central nervous sys
tem remains unclear. The present study examines whether NO plays a rol
e in the regulation of neuronal activity in the nucleus tractus solita
rius (NTS). Single-unit extracellular recordings were obtained from NT
S neurons in slices (400 mu m) of the rat brainstem, which had spontan
eous discharges at a frequency of 0.5 to 3 spikes per second. Eighty-o
ne neurons were tested for sensitivity to L-arginine, which is the phy
siological precursor of NO. L-Arginine (10(-7) to 10(-4) mol/L) increa
sed neuronal activity dose dependently in 33 (40.7%) of 81 neurons tes
ted, but D-arginine (10(-5) mol/L) did not. The neurons that responded
to L-arginine responded to glutamate as well. N-G-Monomethyl-L-argini
ne (10(-5) to 3 x 10(-5) mol/L), an inhibitor of the formation of NO,
dose-dependently blocked increases in the neuronal activity evoked wit
h L-arginine (10(-5) mol/L). Hemoglobin (1.5 mg/L), a trapper of NO, a
nd methylene blue (10(-5) mol/L), an inhibitor of guanylate cyclase, a
lso blocked increases in the neuronal activity evoked with L-arginine
(10(-5) mol/L). Sodium nitroprusside (SNP, 10(-5) to 10(-4) mol/L), wh
ich spontaneously produces NO, increased the neuronal activity in the
neurons that responded to L-arginine. SNP did not alter the neuronal a
ctivity of the neurons that did not respond to L-arginine. Methylene b
lue (10(-5) mol/L) blocked increases in the neuronal activity evoked w
ith SNP (10(-5) mol/L), but hemoglobin did not. These results suggest
that NO is formed from L-arginine in the NTS neurons and that NO incre
ases the neuronal activity of adjacent neurons in the NTS through an i
ncrease in cGMP.