Adenosine deaminase and adenosine uptake inhibitions facilitate ventilation in rats

The effects of intracarotid (i.c.) infusions of the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and of the adenosine uptake blocker, dipyridamole on spontaneous ventilation were studied in rats anaesthetized with sodium pentobarbitone. Both EHNA and dipyridamole mimicked the excitatory effect of adenosine on respiration increasing 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 nerves. The excitatory effect of EHNA on respiration was prevented by adenosine deaminase and antagonized by 1,3-dipropyl-8(p-sulfophenyl)xanthine (DPSPX). DPSPX also antagonized the excitatory effect of dipyridamole on respiration. Both EHNA and dipyridamole in doses virtually devoid of effect on respiration potentiated the excitatory effect of exogenous adenosine on respiration. Two different effects on respiration were observed during i.c. infusions of cumulative doses of DPSPX: one inhibitory, not present in glomectomized animals and another, excitatory, present in both glomectomized and non-glomectomized animals. It is concluded that endogenous adenosine could be involved in respiration mediated through carotid body chemoreceptors and that the nucleoside is inactivated at this level by deamination and uptake.