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gorzata Szereda-Przestaszewska1
ska1
1 Laboratory of Respiratory Reflexes, PAS Medical Research Center, 5 Pawi
skiego Street, 02–106 Warsaw, Poland
The respiratory effects resulting from stimulation of 5-HT1A receptors were studied in spontaneously breathing rats that were: (i) neurally intact and subsequently bilaterally vagotomized; (ii) subjected to bilateral midcervical vagotomy followed by supranodosal vagotomy; (iii) midcervically vagotomized and treated by carotid sinus/body denervation; or (iv) subjected to infra- and supranodosal vagotomy followed by pharmacological blockade of 5-HT1A receptors. An intravenous bolus of the 5-HT1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 10 µg kg–1) evoked increases in both breathing rate and tidal volume. After section of the midcervical and supranodosal vagi, 8-OH-DPAT challenge still increased the respiratory rate and tidal volume. Carotid sinus/body denervation did not reduce the augmentation of the tidal volume, but prevented the increase in breathing rate. Blockade of 5-HT1A receptors with intravenous doses of 1-(2-metoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine (NAN 190; 20 µg kg–1) abolished all respiratory effects of 8-OH-DPAT challenge. In all the neural states, 8-OH-DPAT evoked a significant fall in mean arterial blood pressure. Pretreatment with NAN 190 reduced baseline values of mean arterial pressure and prevented 8-OH-DPAT-induced hypotension. These results indicate that: (i) 8-OH-DPAT-evoked activation of 5-HT1A receptors increases breathing rate and tidal volume, which persists after section of the lung vagi and the nodose ganglia, but only the increase in breathing rate was abolished by carotid sinus/body denervation; and (ii) 8-OH-DPAT hyperventilatory and hypotensive responses result from the excitation of presumed 5-HT1A carotid receptors and the central 5-HT1A-expressing neurones.
(Received 14 February 2007;
accepted after revision 24 May 2007; first published online 25 May 2007)
Corresponding author M. Szereda-Przestaszewska: Laboratory of Respiratory Reflexes, PAS Medical Research Center, 5 Pawi
skiego Street, 02–106 Warsaw, Poland. Email: szereda{at}cmdik.pan.pl
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