title: Central 5-HT(2A) receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats.
abstract: Activation of 5-hydroxytryptamine (5-HT) 5-HT(1A), 5-HT(2C), 5-HT(3), and 5-HT(7) receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT(2A/2B) receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT(2A/2B) antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT(2A) antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT(2B) antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT(2A) receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT(2B) receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT(2A) receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.
authors.affiliation: Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: H A
authors.initials: HA
authors.lastname: Futuro Neto
authors.forename: S M
authors.initials: SM
authors.lastname: Macedo
authors.forename: N F
authors.initials: NF
authors.lastname: Silva
authors.forename: A M
authors.initials: AM
authors.lastname: Cabral
authors.forename: J G P
authors.initials: JG
authors.lastname: Pires
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012018:Reflex / Q000187:drug effects* / Q000528:radiation effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D001645:Biguanides; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D001262:Atenolol; C008846:phenyl biguanide