Received February 14, 2007
Revised March 12, 2007
Accepted after revision May 24, 2007

Magorzata Szereda-Przestaszewska ^1* Katarzyna Kaczyska ²

¹ Polish Academy of Sciences Medical Research Center
² PAS Medical Research Centre

^* To whom correspondence should be addressed. E-mail: szereda{at}cmdik.pan.pl.

	Abstract

The respiratory effects due to 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, and (iv) subjected to infra- and supra-nodose vagotomy followed by pharmacological blockade of 5-HT1A receptors. An intravenous bolus of the 5-HT1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 10µg.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 NAN 190 (20 µg.kg-1) abolished all respiratory effects due to 8-OH-DPAT challenge. In all the neural states, 8-OH-DPAT evoked a significant fall in mean arterial blood pressure. NAN 190 pre-treatment 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. Key words: pattern of breathing; 8-OH-DPAT; 5-HT1A receptors; lung afferents; nodosal vagal afferents; carotid sinus/body afferents

Key Words: Lung, Respiratory control, Serotonin