Studies on the site and mechanism of the sympatholytic action of 8-OH DPAT.
Studies in our laboratory indicate that the 5-HT1A agonist 8-OH DPAT acts in the central nervous system at postsynaptic receptor sites to inhibit sympathetic nerve activity and lower arterial blood pressure. The present study was designed to investigate possible postsynaptic sites on central sympathetic neurons where 8-OH DPAT might produce its sympatholytic action in anesthetized cats. The sympatholytic effect of 8-OH DPAT was compared in midcollicular transected and sham operated control animals. Administration of 8-OH DPAT (0.01-1.0 mg/kg, i.v.) inhibited sympathetic activity and decreased blood pressure in both the transected and sham animals to a similar degree. The effects of microiontophoretically applied 8-OH DPAT and 5-HT on antidromically identified sympathetic preganglionic neurons were determined. Microiontophoretically applied 5-HT consistently increased the firing rate of sympathetic preganglionic neurons. Iontophoretic 8-OH DPAT failed to affect the firing of sympathetic preganglionic neurons but blocked the excitatory effects of 5-HT. The effects of 8-OH DPAT and 5-HT on the firing of sympathoexcitatory neurons located in the rostral ventrolateral medulla were also determined. Sympathoexcitatory neurons were identified using spike triggered averaging techniques and by their response to baroreceptor activation. Intravenous administration of 8-OH DPAT inhibited the firing of sympathoexcitatory neurons in the rostral ventrolateral medulla. The inhibition of unit firing produced by 8-OH DPAT was exactly paralleled by the shutoff of inferior cardiac nerve activity. Microiontophoretic application of 8-OH DPAT and 5-HT onto sympathoexcitatory neurons in the rostral ventrolateral medulla failed to affect the firing rate of these neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Clement
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Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
McCall
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D013565:Sympatholytics; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin