[Alpha-methyldopa and brain monoamines].
Alpha-methyldopa (alpha-MDP) is a widely used hypotensive agent, and it is considered to act on the central nervous system. In the present study, 6-hydroxydopa (6-OHDP) was injected into spontaneously hypertensive rats in a dose of 50 mg/kg on the 19th and 21st days of gestation. Dopamine contents were not changed, but norepinephrine (NE) decreased at 12 weeks of age. When the effect of alpha-MDP was examined at the age of 30 to 40 weeks, the decrease in blood pressure induced by 300 mg/kg alpha-MDP i.p. was significantly attenuated in the 6-OHDP treated rats. Whenever the hypotensive effects of alpha-MDP were inhibited, production of alpha-methylnorepinephrine (alpha-MNE) was markedly reduced only in the spinal cord. 6-Hydroxydopamine (6-OHDA) was also injected into the spinal cord at the C4 level. Although alpha-MDP lowered blood pressure in both 6-OHDA treated and non-treated control rats, the decreased in 6-OHDA treated rats tended to be less pronounced. The accumulation of alpha-MNE in the caudal area of the spinal cord was markedly reduced. Furthermore, in order to destroy the spinal serotonergic neurons selectively, we used intraspinal 5,7-dihydroxytryptamine (5,7-DHT) in the same manner as 6-OHDA injection. In 5,7-DHT treated rats, the blood pressure was decreased fully. These observations seem sufficient to hypothesize, although not to conclude, that the effect of alpha-MDP on the blood pressure is dependent at least partly on the biotransformation to alpha-MNE in the spinal noradrenergic neurons.
D000818:Animals; D000959:Antihypertensive Agents; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008750:Methyldopa / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D008771:Nordefrin / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism; D013563:Sympathectomy, Chemical
D000959:Antihypertensive Agents; D002395:Catecholamines; C001388:6-hydroxydopa; D008750:Methyldopa; D004295:Dihydroxyphenylalanine; D008771:Nordefrin