Evidence for a role for central 5-HT2B as well as 5-HT2A receptors in cardiovascular regulation in anaesthetized rats.
1. The effects of injections i.c.v. of quipazine, (2 micromol kg-1) and 1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane (DOI; 2 micromol kg-1) on renal sympathetic and phrenic nerve activity, mean arterial blood pressure (MAP) and heart rate were investigated in alpha-chloralose anaesthetized rats pretreated with a peripherally acting 5-HT2 receptor antagonist. 2. Quipazine or DOI caused a rise in MAP which was associated with a tachycardia and renal sympathoinhibition in rats pretreated (i.c.v.) with the antagonist vehicle 10% PEG. These effects of quipazine were completely blocked by pretreatment with cinanserin (a 5-HT2 receptor antagonist) and attenuated by spiperone (a 5-HT2A receptor antagonist). However, pretreatment with SB200646A (a 5-HT2B/2C receptor antagonist) only blocked the sympathoinhibition, while pretreatment with SB204741 (a 5-HT2B receptor antagonist) reversed the sympathoinhibition to excitation as it also did for DOI. Quipazine also caused renal sympathoexcitation in the presence (i.v.) of a vasopressin V1 receptor antagonist. 3. Injection (i.v.) of the V1 receptor antagonist at the peak pressor response evoked by quipazine alone and in the presence of SB204741 caused an immediate fall in MAP. For quipazine alone the renal sympathoinhibition was slowly reversed to an excitation, while the renal sympathoexcitation observed in the presence of SB204741 was potentiated. In both, the quipazine-evoked tachycardia was unaffected. 4. The data indicate that cardiovascular responses caused by i.c.v. quipazine and DOI are primarily due to activation of central 5-HT2A receptors, which causes the release of vasopressin and a tachycardia. This released vasopressin appears to suppress a 5-HT2A receptor-evoked central increase in sympathetic outflow, which involves the activation of central 5-HT2B receptors indirectly by the released vasopressin.
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Department of Pharmacology, University College London, Royal Free Campus, Rowland Hill Street, Hampstead, London NW3 2PF.
Ramage
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D000578:Amidines / Q000008:administration & dosage / Q000494:pharmacology; D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001286:Atropine Derivatives / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002928:Cinanserin / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D011814:Quipazine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013134:Spiperone / Q000008:administration & dosage / Q000494:pharmacology
D000578:Amidines; D000662:Amphetamines; D065092:Antidiuretic Hormone Receptor Antagonists; D001286:Atropine Derivatives; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D011092:Polyethylene Glycols; D011814:Quipazine; D013134:Spiperone; C029751:BW 501C; C006649:methylatropine; D002928:Cinanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine