Baroreceptor reflex inhibition induced by the stimulation of serotonin3 receptors in the nucleus tractus solitarius of the rat.
Previous studies suggested that in the nucleus tractus solitarius, cardiovascular responses to serotonin may involve the simultaneous activation of more than one receptor subtype. In the present study, the cardiovascular effects of the local application of serotonin and different serotonin3 agonists and antagonists into the nucleus tractus solitarius were analysed in intact and unilaterally ganglionectomized rats. Unilateral injections of serotonin (5-15 nmol) produced a dose-dependent increase in blood pressure and partially antagonized the arterial baroreflex responses evoked by an i.v. injection of phenylephrine. Similar blood pressures response were obtained after unilateral microinjections of phenylbiguanide (5 nmol) and 2-methyl-serotonin (5 nmol), two serotonin3 receptor agonists. Bilateral microinjections of serotonin or phenylbiguanide produced more pronounced blood pressure effects and antagonized completely the baroreflex responses. Both blood pressure and baroreflex effects were antagonized by prior injections of specific serotonin3 antagonists such as zacopride (100 pmol) and ondansetron (100 pmol). Concomitant autoradiographic studies performed in intact and ganglionectomized rats, using [125I]iodozacopride, confirmed that serotonin3 receptors in the nucleus tractus solitarius are mainly located on vagal afferent fibers. In addition, serotonin microinjections made in the nucleus tractus solitarius ipsilateral to the ganglionectomy revealed a significant reduction in cardiovascular responses compared to intact animals. These results suggest that in the nucleus tractus solitarius of the rat, serotonin is involved in the reflex regulation of blood pressure through the stimulation of serotonin3 receptors presumably located on vagal afferent fibers. Since bicuculline antagonized the serotonin-mediated pressor responses, a serotonin3-dependent activation of an inhibitory GABAergic system within the nucleus tractus solitarius might be involved in blood pressure regulatory mechanisms.
INSERM U288, Neurobiologie Cellulaire et Fonctionnelle, CHU Pitié-Salpêtrière, Paris, France.
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Merahi
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Orer
A M
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Laporte
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Gozlan
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Hamon
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Laguzzi
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D058787:GABA-A Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013268:Stimulation, Chemical
D000317:Adrenergic alpha-Antagonists; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D058787:GABA-A Receptor Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C055971:zacopride