Ventilatory effects of adenosine mediated by carotid body chemoreceptors in the rat

The effects of intracarotid injections of adenosine and adenosine analogues [5'-N-ethylcarboxamidoadenosine (NECA), 2-chloroadenosine (CADO), L-N6-phenylisopropyladenosine (L-PIA) and D-N6-phenylisopropyladenosine (D-PIA)] on ventilation were studied in rats anaesthetized with sodium pentobarbitone or urethane. Adenosine and its analogues increased in a dose-dependent manner respiratory ventilation determined as increases in tidal volume (VT), respiratory frequency (f) and minute volume (VE). These excitatory effects were abolished after section of the carotid sinus nerve. The order of potency of the adenosine analogues was NECA greater than CADO greater than D-PIA, L-PIA, and no marked stereoselectivity was found for the PIA isomers. The methylxanthine, theophylline, in a dose that did not modify respiratory ventilation, antagonized the excitatory action of CADO. An inhibitory, delayed and long-lasting effect of L-PIA on respiration was also observed after its intravenous administration, an effect which was not prevented by section of the carotid sinus nerves. It is concluded that adenosine can have both excitatory and inhibitory effects on ventilation, and that its excitatory effect mediated through carotid body chemoreceptors involves an A2 adenosine receptor.