title: 5-HT-mediated inhibition of cardiovagal baroreceptor reflex response during defense reaction in the rat.
abstract: Previous studies showed that the cardiac response of the baroreceptor reflex (bradycardia) is inhibited during the defense reaction evoked by direct electrical or chemical stimulation of the periaqueductal gray (dPAG) in the rat. Whether central serotonin and nucleus tractus solitarius (NTS) serotonin(3) (5-HT(3)) receptors might participate in this inhibition was investigated in urethane-anesthetized and atenolol-pretreated rats. Our results showed that both electrical and chemical stimulation of the dPAG produced a drastic reduction of the cardiovagal component of the baroreceptor reflex triggered by either intravenous administration of phenylephrine or aortic nerve stimulation. This inhibitory effect of dPAG stimulation on the baroreflex bradycardia was not observed in rats that had been pretreated with p-chlorophenylalanine (300 mg/kg ip daily for 3 days) to inhibit serotonin synthesis. Subsequent 5-hydroxytryptophan administration (60 mg/kg ip), which was used to restore serotonin synthesis, allowed the inhibitory effect of dPAG stimulation on both aortic and phenylephrine-induced cardiac reflex responses to be recovered in p-chlorophenylalanine-pretreated rats. On the other hand, in nonpretreated rats, the inhibitory effect of dPAG stimulation on the cardiac baroreflex response could be markedly reduced by prior intra-NTS microinjection of granisetron, a 5-HT(3) receptor antagonist, or bicuculline, a GABA(A) receptor antagonist. These results show that serotonin plays a key role in the dPAG stimulation-induced inhibition of the cardiovagal baroreceptor reflex response. Moreover, they support the idea that 5-HT(3) and GABA(A) receptors in the NTS contribute downstream to the inhibition of the baroreflex response caused by dPAG stimulation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U.288, CHU Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Comet
authors.forename: Caroline
authors.initials: C
authors.lastname: Sévoz-Couche
authors.forename: Naïma
authors.initials: N
authors.lastname: Hanoun
authors.forename: Michel
authors.initials: M
authors.lastname: Hamon
authors.forename: Raul
authors.initials: R
authors.lastname: Laguzzi
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000374:Aggression / Q000502:physiology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D004558:Electric Stimulation; D010134:Fenclonine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001640:Bicuculline; D010134:Fenclonine; D018756:GABA Antagonists; D017829:Granisetron; D010656:Phenylephrine; D011963:Receptors, GABA-A; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D012702:Serotonin Antagonists