Depletion of brainstem epinephrine stores by α-methyldopa: Possible relation to attenuated sympathetic outflow

Abstract

The antihypertensive effect of α-methyldopa (MD) is believed to be critically dependent on its ability to deplete endogenous catecholamines or cause the synthesis of false neurotransmitters. We used liquid chromatography with electrochemical detection (LCEC) and negative chemical ionization gas chromatography-mass spectrometry (GC-MS) for quantitation of catecholamines and MD metabolites in rat. MD intraperitoneally (100 mg/kg q12 hr × 12 days), significantly increased α-methylnorepinephrine (MNE) in brain (1.02 ± 0.33 μg/g), heart (1.67 ± 0.57 μg/g) and adrenal glands (114.93 ± 50.47 μg/g) Endogenous norepinephrine (NE), epinephrine (E) and dopamine (DA) were reduced. ME levels were 2.19 ± 0.44 μg/g (n=6) in the adrenal gland but only 99 ± 26 pg/g (n=3) in the brainstem. MD-induced endogenous brainstem NE depletion was more than compensated by MNE production, but brainstem E depletion was not compensated for by a stoichiometric production of brainstem ME.