Bulbospinal serotonin neurons and hypotensive effects of methyldopa in the spontaneously hypertensive rat.
Systemic methyldopa administration in genetically hypertensive rats evoked a hypotension which was attenuated after prior treatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) given either intracerebroventricularly, to produce a generalised ablation of serotonin nerves in brain and spinal cord, or by injection into the cervical spinal cord, to cause a selective destruction of descending serotonin pathways. Direct microinjection of methyldopa into the ventrolateral medulla in the area of the B1 and B3 serotonin cells was also effective in lowering arterial pressure. The hypotensive response to this medullary administration of methyldopa was again attenuated by 5,7-DHT given either intracerebroventricularly or by intraspinal injection. On the other hand, prior treatment intracerebroventricularly with 6-hydroxydopamine did not affect the hypotensive effect of methyldopa injected into the region of the ventrolateral B1 and B3 cells, supporting the suggestion that this effect of methyldopa is mediated by bulbospinal serotonin neurons and not by descending catecholamine nerves. The fact that methyldopa injection into the ventrolateral medulla in a region coinciding with the B1 and B3 cells lowers blood pressure is consistent with previous studies demonstrating that these neurons serve to maintain or elevate arterial pressure.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008750:Methyldopa / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D006892:Hydroxydopamines; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D008750:Methyldopa; D016627:Oxidopamine