Neurochemistry of the sympathoadrenal pathway activated by hydralazine induced hypotension

Hydralazine and sodium nitroprusside have been used to identify neurons activated by lowering blood pressure. Such hypotensive stimuli can however evoke hyperglycemia. The aim was to identify the neurochemistry and identity of cells activated in the spinal cord and adrenal medulla in response to hydralazine. Multilabel immunoreactivity (ir) in combination with in situ hybridization was used to identify activated cells and their neurochemistry following 10 mg/kg i.p. hydralazine (HDZ) or saline. 16 ± 0.1% (n = 3) of ChAT-ir sympathetic preganglionic neurons (SPN) contained c-Fos-ir following HDZ whereas following saline no SPN were activated. Blood glucose levels were 23.8 ± 2.8 mmol/L (HDZ, n = 7) and 10.6 ± 0.8 mmol/L (saline, n = 7 p < 0.001) whereas plasma adrenaline levels were similar between the two conditions (0.4 ± 0.2 ng/ml; n = 7 and 0.5 ± 0.1 ng/ml; n = 7) and plasma noradrenaline levels were increased following HDZ (1.3 ± 0.3 ng/ml; n = 5; vs saline 0.4 ± 0.1 ng/ml; n = 5 p < 0.01). 62.8 ± 1.4% of SPN projecting to the adrenal gland (n = 3) and 53.2 ± 8.6% of SPN projecting to the celiac ganglia (n = 3) contained c-Fos-ir after HDZ injection. Of activated SPN that projected to the adrenal gland 29.9 ± 3.3% and 31.2 ± 8.8% of activated SPN that projected to the celiac ganglia expressed PPE mRNA. We have previously demonstrated that 100% of adrenally projecting SPN that expressed PPE mRNA were activated by a glucoprivic stimulus that activated adrenaline but not noradrenaline releasing chromaffin cells (Parker et al 2013). Together these results indicate that SPN activated by blood pressure lowering stimuli include those that innervate adrenaline releasing chromaffin cells. However HDZ did not evoke c-Fos -ir in adrenal chromaffin cells nor did it phosphorylate serine residues of the tyrosine hydroxylase enzyme in the adrenal medulla which increase enzyme activity or plasma adrenaline. Thus HDZ did not activate the adrenal medulla despite the fact that adrenally projecting SPN were activated.