Ascending noradrenergic projections from the brainstem: evidence for a major role in the regulation of blood pressure and vasopressin secretion.

Abstract

The role of projections from the lateral tegmental (A1, A2) and coeruleal (A6) noradrenergic cell groups in the control of arginine vasopressin (AVP) secretion was studied following lesions to the ventral (VNAB) and dorsal (DNAB) noradrenergic bundles by 6-hydroxydopamine. These lesions were associated with the expected, large reductions in cortical (DNAB) and hypothalamic (VNAB) noradrenaline concentrations. Vehicle injected, control animals and VNAB lesioned animals showed a similar AVP secretory response to haemorrhage, whilst the DNAB group showed a markedly diminished release of AVP in response to this challenge. Following Clonidine injection, both controls and VNAB animals showed major reductions in plasma AVP concentrations, but again the DNAB group behaved in a different manner, with a marked attenuation of the inhibitory effect of Clonidine on AVP secretion. In addition, the DNAB group had a significantly lower basal blood pressure, a greater initial agonist response to Clonidine and a loss of the hypotensive response to Clonidine in comparison to sham and VNAB lesioned groups. All three groups showed a similar AVP response to intravenous nicotine. These data suggest that noradrenergic projections originating in the locus coeruleus, or in the lateral tegmental NA groups but which ascend together with coeruleal axons in the DNAB, modulate the vasopressin response to visceral stimuli and to Clonidine, and that they also play an important role in mediating the hypotensive effect of Clonidine.