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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.
AuthorsH A Futuro Neto, S M Macedo, N F Silva, A M Cabral, J G P Pires
JournalBrazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 44 Issue 3 Pg. 224-8 (Mar 2011) ISSN: 1414-431X [Electronic] Brazil
PMID21344136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics
  • Biguanides
  • Receptor, Serotonin, 5-HT2A
  • Serotonin Receptor Agonists
  • Atenolol
  • phenyl biguanide
Topics
  • Analgesics (pharmacology)
  • Animals
  • Atenolol (pharmacology)
  • Biguanides (pharmacology)
  • Bradycardia (chemically induced, physiopathology)
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A (physiology)
  • Reflex (drug effects, radiation effects)
  • Serotonin Receptor Agonists (pharmacology)
  • Vagus Nerve (drug effects, physiopathology)

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