Paraventricular nucleus activation of renal sympathetic neurones is synaptically depressed by nitric oxide and glycine acting at a spinal level

Abstract

A high density of nitric oxide synthesising enzyme is present in sympathetic preganglionic neurones in the spinal cord. It has been shown that nitric oxide is released as a consequence of synaptic activity. In the present study in anaesthetised rats we determined if nitric oxide acted as a retrograde messenger molecule to modulate the excitatory effects on the renal sympathetic spinal network elicited by paraventricular nucleus stimulation. Neurones in the latter nucleus were stimulated by microinjecting DLH and drugs were applied to the spinal cord via an intrathecal catheter with the tip positioned at T 9–T 10. Intrathecal application of the nitric oxide donors, sodium nitroprusside or [3-(2-hydroxy-1-methyl-2-nitrosohydrazino)- N-methyl-1-propanamine] significantly increased tonic activity in the renal sympathetic nerve. In contrast synaptic activity evoked by intrathecal glutamate or by paraventricular nucleus stimulation was enhanced by preventing nitric oxide generation with intrathecal N G-monomethyl- l-arginine monoacetate ( l-NMMA) a nitric oxide synthase inhibitor. Enhancement of synaptically induced renal nerve activity was also observed following intrathecal glycine receptor inhibitor strychnine. Strychnine was without effect when it was given after l-NMMA. It was concluded that paraventricular nucleus excitation of renal sympathetic neurones is subject to inhibitory modulation by released nitric oxide and it is suggested the latter acts via glycine interneurones.