Activation of nucleus tractus solitarius 5-HT2A but not other 5-HT2 receptor subtypes inhibits the sympathetic activity in rats.
Our first aim was to elucidate the mechanisms underlying the hypotensive response elicited by 5-HT(2) receptor activation in the nucleus tractus solitarius (NTS). In pentobarbitone-anaesthetized rats, intra-NTS administration of 2,5-dimethoxy-4-iodoamphetamine (DOI), a wide spectrum 5-HT(2) receptor agonist, but not an antagonist of selective 5-HT(2B) and 5-HT(2C) receptors, produced a decrease in blood pressure and heart rate. The maximal cardiovascular changes obtained by DOI (0.5 pmol) could be almost completely abolished by prior intra-NTS microinjection (10 pmol) of MDL-100907, a selective 5-HT(2A) receptor antagonist, but not by 5-HT(2B) or 5-HT(2C) receptor antagonists. In addition, using extracellular recordings we found that the large majority of identified cardiovascular rostroventrolateral medulla (RVLM) neurons were almost totally inhibited by NTS 5-HT(2A) receptor stimulation. We then investigated whether intra-NTS administration of a subthreshold dose (0.05 pmol) of DOI, known to facilitate the cardiovagal component of the baroreflex, could also modulate the sympathoinhibitory component of this reflex. These experiments showed that neither the decrease in the activity of the cardiovascular RVLM neurons and lumbar sympathetic nerve activities produced by aortic occlusion (gain of the baroreflex), nor the hypotensive response elicited by aortic nerve stimulation, were potentiated by the microinjection of DOI under such conditions. These data show that activation of 5-HT(2A), but not 5-HT(2B) or 5-HT(2C), receptors, located on NTS neurons, elicits depressor and bradycardic responses, and that this 5-HT(2A)-mediated hypotension is produced via the inhibition of RVLM cardiovascular neurons. In addition, NTS 5-HT(2A) receptor activation facilitates the cardiac but not the sympathetic baroreflex response.
Comet
M-A
MA
Université Pierre et Marie Curie-Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, IFR 70 des Neurosciences, UMR S677, F-75013 Paris, France.
Bernard
J F
JF
Hamon
M
M
Laguzzi
R
R
Sévoz-Couche
C
C
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013876:Thiophenes / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D000319:Adrenergic beta-Antagonists; D001286:Atropine Derivatives; D007211:Indoles; D011719:Pyrazines; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; D001262:Atenolol; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C006649:methylatropine