Evidence that activation of central 5-HT(2B) receptors causes renal sympathoexcitation in anaesthetized rats.
The effects of injections i.c.v. of alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (BW723C86; 0.02 - 2 micromol kg(-1)), a 5-HT(2B) receptor agonist, on renal sympathetic and phrenic nerve activity, mean arterial blood pressure and heart rate were investigated in alpha-chloralose anaesthetized rats pretreated with a peripherally acting 5-HT(2) receptor antagonist. BW723C86 i.c.v. caused a dose-related increase in renal nerve activity reaching a maximum of 67+/-6%, which at the highest dose was associated with a small and maintained fall in mean arterial blood pressure of 7+/-3 mmHg. These changes were not associated with any significant changes in heart rate or phrenic nerve activity. BW723C86-evoked increases in renal nerve activity and hypotension were attenuated by pretreatment (i.c.v.) with SB204741 (300 nmol kg(-1); a 5-HT(2B) receptor antagonist) but not by the same dose (i.c.v.) of ketanserin (a 5-HT(2A) receptor antagonist) or RS102221 (a 5-HT(2C) receptor antagonist). None of these antagonists alone had any effect on the variables being measured. It is concluded that central 5-HT(2B) receptors may play a selective role in the control of sympathetic supply to the kidney, which could be important in the central mechanisms involved in blood volume regulation. British Journal of Pharmacology (2000) 129, 177 - 183
Knowles
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ID
Department of Pharmacology, University College London, Royal Free Campus, Rowland Hill Street, Hampstead, London, UK.
Ramage
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AG
D000578:Amidines / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D007650:Ketanserin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D013268:Stimulation, Chemical; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013876:Thiophenes / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000578:Amidines; D007211:Indoles; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D013449:Sulfonamides; D013876:Thiophenes; C029751:BW 501C; D007650:Ketanserin