Hypotensive effects of 5-HT1A receptor activation: ventral medullary sites and mechanisms of action in the rat.
Serotonin-1A (5-HT1A) binding sites were previously localized in several regions of the ventral medulla associated with neural regulation of the cardiovascular system. Some of these binding sites were associated with serotonergic neurons of the ventral medulla. The purpose of these studies was to assess and characterize hypotensive responses to a 5-HT1A agonist, (8-hydroxy-dipropylaminotetraline, 8-OH-DPAT), administered to the ventral medulla of the rat, to correlate the responsive ventral medullary sites with the distribution of 3H-8-OH-DPAT binding sites, and to assess the role of serotonergic systems in mediating the hypotensive responses. Ventral medullary application of 8-OH-DPAT caused dose-related reductions in mean arterial pressure and heart rate which were mediated by the autonomic nervous system. The hypotensive response to 8-OH-DPAT was attenuated by pretreatment with the 5-HT1A antagonists, spiperone or NAN-190. Microinjections of 8-OH-DPAT into ventral medullary structures revealed that 8-OH-DPAT responsive sites included the raphe pallidus, the parapyramidal region, and the rostral ventrolateral medulla. The role of serotonergic terminals in mediating the responses of 8-OH-DPAT was evaluated in animals pretreated with the serotonin nerve toxin, 5,7-dihydroxytryptamine (5,7-DHT). Cardiovascular responses to ventral medullary application of 8-OH-DPAT were unaffected by the selective depletion of serotonin. Thus, whereas the hypotensive responses elicited by 8-OH-DPAT in the raphe pallidus and parapyramidal region may involve serotonergic neurons, other non-serotonergic sites (e.g. the rostral ventrolateral medulla) can mediate the hypotensive actions of 8-OH-DPAT.
Helke
C J
CJ
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
McDonald
C H
CH
Phillips
E T
ET
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001340:Autonomic Nerve Block; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin