Characterization of the effects of activation of ventral medullary serotonin receptor subtypes on cardiovascular activity and respiratory motor outflow to the diaphragm and larynx.
The purpose of the present study was to characterize the cardiorespiratory effects of activation of 5-HT1A, 5-HT1B and 5-HT2 receptor subtypes at the intermediate area of the ventral surface of the medulla. The agonists (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OH-DPAT), 1-[3-(trifluoromethyl)phenyl]-piperazine hydrochloride (TFMPP) and (+/-)-1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were used to activate these receptor subtypes, respectively. Application of each drug to the intermediate area produced a different profile of cardiorespiratory effects. 8-OH-DPAT (0.0625-4.0 micrograms) produced dose-dependent hypotension and bradycardia, which were antagonized by the 5-HT1A antagonists spiperone and spiroxatrine. The bradycardia was blocked by bilateral vagotomy. No significant changes in respiratory motor outflow to the larynx or diaphragm were observed after application of 8-OH-DPAT. TFMPP (10-1000 micrograms) also produced a dose-dependent hypotension and bradycardia. However, these effects were not antagonized by spiperone or blocked by vagotomy. A decrease in the amplitude of the recurrent laryngeal and phrenic nerve signals was observed after application of the highest dose of TFMPP. In contrast to the effects of 8-OH-DPAT and TFMPP, DOI (0.3-100 micrograms) produced an increase in blood pressure without any change in heart rate. Recurrent laryngeal and phrenic nerve activities were depressed, as was respiratory rate, after application of DOI. Both the cardiovascular and respiratory effects of DOI were blocked by the 5-HT2 antagonist ketanserin. These results indicate that activation of ventral medullary 5-HT receptor subtypes produces unique effects on cardiorespiratory activity.
King
K A
KA
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington.
Holtman
J R
JR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007823:Laryngeal Nerves / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012009:Recurrent Laryngeal Nerve / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C018406:1-(3-trifluoromethylphenyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine