Stimulation of 5-HT3 receptors in the NTS inhibits the cardiac Bezold-Jarisch reflex response.
Intra-atrial administration of phenylbiguanide has been shown to trigger, through the stimulation of vagal afferent C-fibers, reflex bradycardia, hypotension, and sympathoinhibition classically known as the Bezold-Jarisch (B-J) reflex (O. Krayer. Naunyn-Schmiedeberg's Arch. Exp. Pathol. Pharmacol. 240: 361-368, 1961). The effects of microinjections, into the nucleus tractus solitarius (NTS), of serotonin (5-HT) and 1-(m-chlorophenyl)-biguanide (CPBG), a potent 5-HT3 receptor agonist, on these reflex responses were studied in urethananesthetized rats. 5-HT (600 and 900 pmol) and CPBG (10-150 pmol) produced a dose-dependent inhibition of the atropine-sensitive bradycardiac component of the B-J reflex. The effect of both agonists was reversed by prior local microinjection of the 5-HT3 receptor antagonists zacopride (100 pmol) and ondansetron (100 pmol), but not by that of the 5-HT2 receptor antagonist ketanserin (10 pmol) or the mixed 5-HT1/5-HT2 receptor antagonist methysergide (100 pmol). In contrast, CPBG (150 pmol) did not affect the B-J reflex inhibition of lumbar sympathetic nerve discharge. These results show that stimulation of NTS 5-HT3 receptors produced an inhibition of the cardiovagal component of the B-J reflex without affecting its sympathetic component. Because the stimulation of these receptors also inhibits the cardiac component of the baroreflex, the present data suggest the participation of NTS 5-HT3 receptors in the mechanisms that modulate cardiac reflex responses elicited by messages from different vagal afferents.
Sévoz
C
C
Institut National de la Santé et de la Recherche Médicale Unitè 288, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France.
Nosjean
A
A
Callera
J C
JC
Machado
B
B
Hamon
M
M
Laguzzi
R
R
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects
D001645:Biguanides; D018756:GABA Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C065734:1-(3-chlorophenyl)biguanide