Respiratory effects of cyclic AMP following injection into the nucleus tractus solitarius of rats

Rats were anesthetized with urethane and a limited occipital craniotomy was performed to expose the caudal medulla in the region of the obex. Injections were made into sites in the brainstem of spontaneously-breathing rats through glass micropipettes. Tidal volume, respiratory frequency, minute volume, blood pressure and heart rate were recorded before and after the administration of 8-bromoadenosine 3',5'-cyclic monophosphate (Br-cAMP), an analog of cyclic AMP. Injections of Br-cAMP into the ventromedial portion of the caudal nucleus tractus solitarius (NTS) produced dose-related decreases in pulmonary ventilation due to effects on both respiratory frequency, as well as minute volume. In larger doses, Br-cAMP produced periodic apnea and irregular breathing. The respiratory depression was accompanied by transient hypotension and bradycardia. The data indicate that cyclic AMP may function as a second messenger in respiratory control regions in the brainstem.