Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: role of the nucleus tractus solitarius 5-HT2A receptors.
We previously showed that serotonin (5-HT2) receptor activation in the nucleus of the tractus solitarius (NTS) produced hypotension, bradycardia, and facilitation of the baroreflex bradycardia. Activation of the preoptic area (POA) of the hypothalamus, which is involved in shock-evoked passive behaviors, induces similar modifications. In addition, previous studies showed that blockade of the infralimbic (IL) part of the medial prefrontal cortex, which sends projections to POA, produced an inhibitory influence on the baroreflex cardiac response. Thus, to assess the possible implication of NTS 5-HT2 receptors in passive cardiovascular responses, we analyzed in anesthetized rats the effects of NTS inhibition and NTS 5-HT2 receptor blockade on the cardiovascular modifications induced by chemical (0.3 M D,L-homocysteic acid) and electrical (50 Hz, 150-200 microA) stimulation of IL or POA. Intra-NTS microinjections of muscimol, a GABAA receptor agonist, prevented the decreases in blood pressure and heart rate normally evoked by IL or POA activation. In addition, we found that intra-NTS microinjection of R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol, a specific 5-HT2A receptor antagonist, did not affect the decreases in cardiovascular baseline parameters induced by IL or POA stimulation but prevented the facilitation of the aortic baroreflex bradycardia normally observed during IL (+65 and +60%) or POA (+70 and +69%) electrical and chemical stimulation, respectively. These results show that NTS 5-HT2A receptors play a key role in the enhancement of the cardiac response of the baroreflex but not in the changes in basal heart rate and blood pressure induced by IL or POA stimulation.
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UMR 677 INSERM/UPMC, Faculté de Médecine Pierre et Marie Curie-Site Pitié-Salpêtrière, 91 Bd de l'Hôpital, 75634 Paris Cedex 13, France. sevoz@ext.jussieu.fr
Comet
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Bernard
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Hamon
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Laguzzi
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D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology* / Q000502:physiology*; D004558:Electric Stimulation; D005464:Fluorobenzenes / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology; D011301:Preoptic Area / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology; D013268:Stimulation, Chemical; D013565:Sympatholytics / Q000494:pharmacology
D001286:Atropine Derivatives; D005464:Fluorobenzenes; D010276:Parasympatholytics; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D013565:Sympatholytics; D001262:Atenolol; C006649:methylatropine; D007650:Ketanserin; C079049:volinanserin