Effects of serotonin1 and serotonin2 receptor agonists and antagonists on blood pressure, heart rate and sympathetic nerve activity.
Previous studies indicate that serotonin (5-HT) neurons provide a tonic excitatory input to central sympathetic neurons. The purpose of the present study was to utilize a number of 5-HT agonists in order to provide insights into the general function of the serotonergic system in the regulation of central sympathetic pathways. The 5-HT1A agonists 8-hydroxy-dipropylaminotetralin and p-aminophenyl-ethyl-m-trifluoromethylphenyl piperazine produced a dose-related inhibition of sympathetic nerve discharge (SND) recorded from either the postganglionic inferior cardiac nerve or the preganglionic splanchnic nerve in chloralose-anesthetized cats. The sympatholytic effects of 8-hydroxy-dipropylaminotetralin and p-aminophenyl-ethyl-m-trifluoromethylphenyl piperazine were accompanied by hypotension and bradycardia. The effects of 5-HT1A agonists were reversed by the 5-HT1A antagonist spiperone. In contrast, spiperone alone produced decreases in blood pressure, heart rate and SND. The 5-HT1B agonists 1[3(trifluoromethyl) phenyl]-piperazine, 1-(3-chlorophenyl) piperazine and 1-(2-methoxyphenyl) piperazine all produced variable effects on SND. In some experiments, SND was increased by these agents, whereas it was decreased in others. The 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane produced a marked increase in SND. A second 5-HT2 agonist, MK212, produced similar effects. The role of 5-HT receptor subtypes in mediating the 5-HT excitation of sympathetic neurons is discussed. It is suggested that 5-HT1A agonists inhibit SND through a process of disfacilitation by inhibiting the firing rate of 5-HT neurons. Possible mechanisms by which 5-HT2 agonists increase SND are proposed.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D006339:Heart Rate / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D010879:Piperazines; D011719:Pyrazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C018406:1-(3-trifluoromethylphenyl)piperazine; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C044643:LY 165163; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine