Peripheral 5-HT1A receptors are not essential for increased ventilation evoked by systemic 8-OH-DPAT challenge in anaesthetized rats

Abstract

The respiratory effects resulting from stimulation of 5-HT(1A) 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-HT(1A) receptors. An intravenous bolus of the 5-HT(1A) receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 10 microg 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-HT(1A) receptors with intravenous doses of 1-(2-metoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine (NAN 190; 20 microg 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-HT(1A) 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-HT(1A) carotid receptors and the central 5-HT(1A)-expressing neurones.