Ventrolateral medulla: an important site of action for the hypotensive effect of drugs that activate serotonin-1A receptors.
The purpose of our study was to test the hypothesis that drugs that activate the 5-HT1A receptor lower arterial pressure by interacting with 5-HT1A receptors located in the ventrolateral medulla. For this purpose, cats were anesthetized with alpha-chloralose while arterial pressure, heart rate, and several indices of respiratory activity were being monitored during either topical application or microinjection of 5-HT1A receptor agonist and antagonist drugs in the region of the intermediate area of the ventrolateral medulla. Topical application of drugs that activate 5-HT1A receptors (e.g., 8-OH-DPAT and urapidil) produced decreases in arterial pressure, heart rate, and tidal volume but an increase in respiratory rate. These effects were prevented by prior topical application of the 5-HT1A antagonist drug, spiperone. Intravenous administration of 5-HT1A receptor agonist drugs produced similar cardiorespiratory effects, and these effects were counteracted by topical application of spiperone to the intermediate area of the ventrolateral medulla. Microinjection of 8-OH-DPAT into two sites associated with the intermediate area, namely the subretrofacial nucleus and the bicuculline-sensitive hypotensive site, also resulted in decreases in arterial pressure (-40 +/- 10 mm Hg, n = 5; and -21 +/- 4 mm Hg, n = 3, respectively). These data indicate that hypotension produced by drugs that activate 5-HT1A receptors occurs, at least in part, from an action in the ventrolateral medulla, presumably in the subretrofacial nucleus and/or the bicuculline-sensitive hypotensive site.
Mandal
A K
AK
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007.
Zhong
P Y
PY
Kellar
K J
KJ
Gillis
R A
RA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000287:Administration, Topical; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D013990:Tidal Volume
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin