The cardiovascular effects of quipazine are mediated by peripheral 5-HT2 and 5-HT3 receptors in anaesthetized rats.
Quipazine (0.5-2 mg/kg i.v.) produced transient hypotension and bradycardia followed by sustained hypertension and variable effects on heart rate in anaesthetized rats. The hypotension, bradycardia and sympatho-inhibitory effects of quipazine were attenuated by bivagotomy. In bivagotomized rats, the hypertension produced by quipazine was not modified by hexamethonium or prazosin but was abolished by ritanserin (1 mg/kg i.v.). In ritanserin-treated rats, section of the carotid sinus nerves and vagus nerves or ICS 205.930 (0.1 mg/kg i.v.) abolished the hypotensive, bradycardic and sympatho-inhibitory effects of quipazine; the action of quipazine was not reproducible in these rats. Quipazine also inhibited the Bezold-Jarish reflex elicited by 5-HT (20 micrograms/kg i.v.). In ICS 205.930-treated rats, the hypertension evoked by quipazine was associated with a reduction in splanchnic nerve activity due to stimulation of baroreceptors. The renin-angiotensin system is not involved in the hypertensive response. The increase in heart rate produced by quipazine in bivagotomized rats was reduced by ritanserin and tertatolol (0.1 mg/kg i.v.) and abolished by a combination of both drugs. We conclude that the bradycardic and sympatho-inhibitory effects of quipazine result from activation of 5-HT3 receptors located in the cardiopulmonary area and of carotid body chemoreceptors. The hypertension and tachycardia are mediated by vascular and myocardial 5-HT2 receptors. No evidence was obtained for a central sympatho-excitatory effect.
Vayssettes-Courchay
C
C
Institut de Recherches Servier, Suresnes, France.
Bouysset
F
F
Verbeuren
T J
TJ
Laubie
M
M
Schmitt
H
H
D000578:Amidines / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D016713:Ritanserin; D013564:Sympathetic Nervous System / Q000187:drug effects; D013876:Thiophenes; D000077526:Tropisetron; D014628:Vagotomy
D000578:Amidines; D006584:Hexamethonium Compounds; D007211:Indoles; D010880:Piperidines; D011412:Propanolamines; D011985:Receptors, Serotonin; D013876:Thiophenes; D016713:Ritanserin; D011814:Quipazine; C029751:BW 501C; D000077526:Tropisetron; C005632:tertatolol; D011224:Prazosin