Effect of barodenervation on tyrosine hydroxylase phosphorylation in rat brain following hypotension

Tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis, has three serine residues, Ser19, Ser31 and Ser40, that when phosphorylated are associated with an increase in activity of TH that occurs following the release of catecholamine (in vitro). The aim was to determine the effect of hypotension on TH phosphorylation in the catecholamine cell groups in brain of barointact, sham operated barointact and barodenervated rats (n=30). Male Sprague Dawley rats were chronically barodenervated 1 week prior. 20 minutes after administration of hydralazine (10mg/kg i.p), animals were anaesthetised and brain regions containing the A1, caudal C1, rostral C1, A2/C2, A5, A6, A8/9, A10, nucleus accumbens, prefrontal cortex and striatum were isolated. Western blot analysis using highly specific antibodies against the serine residues was performed. In barointact rats, hydralazine increased pSer19 (4.3 fold), pSer31 (1.6 fold) and pSer40 (2.5 fold) in the caudal C1. In the rostral C1, hydralazine increased pSer19 (2.1 fold) and pSer31 (1.4 fold). In the A6, hydralazine increased in pSer31 (2.5 fold), A8/9 increased in pSer19 (1.9 fold) and A10 increased in pSer19 (3.1 fold) and pSer40 (1.6 fold). In the prefrontal cortex, hydralazine increased pSer31 (8.5 fold). TH in brain cell groups were differentially activated by the stimulus. Our data will compare and contrast findings from the barodenervated group.