Correlation between fall in blood pressure and in vivo amine release after alpha-methylDOPA

Blood pressure (BP), hypothalamic tissue concentrations and the in vivo overflow of endogenous and alpha-methylated catecholamines were measured in urethane anaesthetised rats after alpha-methylDOPA (mDOPA) administration (200 mg/kg i.p.). Four hours after mDOPA, BP fell to its lowest value, 60% of control, and slowly returned towards control levels by 24 h. This was closely correlated with the evoked overflow of alpha-methylnoradrenaline (mNA, r = 0.9) and noradrenaline (NA, r = 0.7) but not dopamine (DA) or alpha-methyldopamine (mDA). However, the tissue content of mNA rose much more gradually and was not maximal until after 12 h while mDA content followed the development of the hypotension. The results provide direct evidence for a false transmitter role for mNA in the brain, and suggest that the release of newly synthesised mNA is responsible for the hypotensive effect of mDOPA. Differences in the time course of overflow and storage of NA and mNA suggest the presence of separate transmitter storage and releasable pools.