Hypotensive effects of 5-HT1A receptor agonists on the ventrolateral medullary pressor area in dogs.
An attempt to determine the central site of the sympathoinhibitory effects of 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, has been made in normotensive anesthetized dogs. Intravenous and central (cisterna magna, vertebral artery) administration of 8-OH-DPAT induced dose-dependent decreases in blood pressure and sympathetic (splanchnic and renal) nerve activity in intact and baroreceptor denervated dogs. In contrast, 8-OH-DPAT was ineffective when injected into the nucleus tractus solitarii or into the raphe nuclei. Administration of 8-OH-DPAT into the ventrolateral pressor area (VLPA) decreased blood pressure and renal sympathetic nerve activity. The sympathoinhibitory effects of 8-OH-DPAT injected into the vertebral artery (v.a.) were antagonized by methiothepin and (+/-)pindolol injected into the v.a. Likewise, the effects of 8-OH-DPAT administered into the VLPA were antagonized by methiothepin injected into the same site. Depletion of central catecholamines and 5-HT content did not change the sympathoinhibitory effects of 8-OH-DPAT. These results suggested that 8-OH-DPAT has a direct effect on 5-HT1A receptors located in the VLPA in dogs.
INSERM U228, Faculté de Médecine, Broussais Hôtel-Dieu, Paris, France.
H
H
Dabiré
M
M
Laubie
H
H
Schmitt
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000502:physiology; D002946:Cisterna Magna; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D007269:Injections, Intra-Arterial; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008781:Methyltyrosines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D019805:alpha-Methyltyrosine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine