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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: role of the nucleus tractus solitarius 5-HT_2A receptors

Unité Mixte de Recherche 677 Institut National de la Santé et de la Recherche Médicale/Université Pierre et Marie Curie, Faculté de Médecine Pierre et Marie Curie- Site Pitié-Salpêtrière, Paris Cedex 13, France

Submitted 20 January 2006 ; accepted in final form 3 May 2006

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 µA) stimulation of IL or POA. Intra-NTS microinjections of muscimol, a GABA_A 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(+)--(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol, a specific 5-HT_2A 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-HT_2A 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.

baroreceptor; peripheral nervous system; prefrontal; preoptic; serotonin; rat