Key result
Activation of 5-HT2A receptors in the nucleus tractus solitarius of rats elicits depressor and bradycardic responses via the inhibition of RVLM cardiovascular neurons.
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Activation of 5-HT2A receptors in the nucleus tractus solitarius lowers blood pressure and heart rate by inhibiting RVLM cardiovascular neurons and facilitates the cardiac baroreflex.
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.
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Comet et al. (2007) studied this question. Intra-NTS administration of DOI (2,5-dimethoxy-4-iodoamphetamine) vs. 5-HT2A, 5-HT2B, or 5-HT2C receptor antagonists was evaluated on Blood pressure, heart rate, and RVLM neuron activity. Activation of 5-HT2A receptors in the nucleus tractus solitarius of rats elicits depressor and bradycardic responses via the inhibition of RVLM cardiovascular neurons.
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