Effects of alpha-methyldopa on systolic pressure and activities of tyrosine hydroxylase, dopamine-beta-hydroxylase and phenethanolamine-N-methyl-transferase in nervous system of spontaneously hypertensive rats

After alpha-methyldopa(MD) sc 50 mg/kg bid x 5 d, the systolic pressure of spontaneously hypertensive rats(SHR) was decreased, while no effect on blood pressure of normotensive rats was seen. Treated with MD,SHR were killed on d 6. The brains, superior cervical ganglions(SCG),and adrenal medulla were excised. The brain slices were punched from locus coeruleus(A6), vasomotor center of medulla oblongata(A1C1,A2C2) and spinal sympathetic laternal column(SLC). The activities of tyrosine hydroxylase(TH),dopamine-beta-hydroxylase(DbetaH) and phenethanolamine-N-methyltransferase(PNMT) were determined by radio-enzymatic methods. The TH activities in A1C1,A2C2, SLC and A6 were increased, whereas no marked effects on the activities of DbetaH and PNMT in them were found. Thus, it indicated that MD &/or its metabolites had a positive feed-back regulation on the TH activity from presynaptic receptor of NA-&/or adrenaline neurons in vasomotor center, SLC and A6.It is surmised that MD &/or its metabolites are antagonists of alpha2-receptors( not agonists) to explain the central hypotensive effect of MD. The DbetaH activity only in adrenal medulla was inhibited by MD. It is suggested that the reduction of peripheral vasotension was in consequence of the lowering contents of NA and Adr in peripheral tissues.