The potential role of the nodose ganglion adenosine A1 receptor in regulation of breathing in anaesthetized rats
The respiratory effects of stimulation of adenosine A1 receptors were studied in spontaneously breathing rats that were either (1) neurally intact and subsequently bilaterally vagotomized in the neck, or (2) neurally intact and subjected to supranodosal vagotomy or (3) midcervically vagotomized before and after pharmacological blockade of A1 receptors. Before neural interventions an intravenous bolus of the A1 receptor agonist N6-cyclopentyladenosine (CPA, 5 µg kg-1) decreased breathing rate, tidal volume, mean arterial blood pressure (MAP) and heart rate. After section of the midcervical vagi, CPA still decreased respiratory rate and tidal volume. Supranodose vagotomy abolished the fall in respiratory rate but did not affect the depression of tidal volume. Blockade of A1 receptors with intravenous doses of DPCPX (100 µg kg-1) eliminated all respiratory effects of CPA challenge. In all the neural states, CPA caused significant falls in mean arterial blood pressure and heart rate. DPCPX pre-treatment prevented these cardiovascular effects. The present data suggest that: (1) CPA-evoked activation of A1 receptors decreases breathing rate and tidal volume and this occurs central to the cervical vagi; (2) supranodosal vagotomy prevents the decrease in breathing rate, which is presumably due to stimulation of nodosal A1 receptor; and (3) depression of tidal volume and the hypotensive response result from the excitation of central nervous A1 expressing neurones.