Purines and the nucleus tractus solitarius: effects on cardiovascular and respiratory function

1. The roles of adenosine and adenosine 5'-triphosphate in cardiorespiratory regulation by the nucleus tractus solitarius (NTS) have been evaluated in a range of experiments, using micro-injections of selective agonists and antagonists of purinoceptors. 2. Adenosine injected into the caudal NTS decreases heart rate (HR), arterial blood pressure (BP) and respiratory frequency by an action at A2a receptors on glutamatergic nerve terminals. Microinjections of the A2a agonist CGS21680 caused falls in arterial BP and HR which were selectively antagonized by the A2a antagonist CGS15943. Injection of the A1 agonist CPA in the caudal NTS elevated BP and HR and its actions were selectively antagonized by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine. Adenosine enhanced glutamate release in the NTS. 3. In the rostral NTS, adenosine administration resulted in an elevation of BP. 4. ATP microinjection into the subpostremal NTS depressed HR and BP by an action on P2x purinoceptors, which are blocked by saramin. ATP microinjections differentially affected vascular conductance in regional peripheral vascular beds, with the most marked increases in conductance in the iliac bed and lesser effects in the superior mesenteric and renal vascular beds. 5. Recordings from renal and lumbar sympathetic nerves have demonstrated marked dose-dependent decreases in efferent activity following alpha, beta-methylene ATP injections into the NTS; however, only renal but not lumbar sympathetic nerve activity was inhibited following CGS21680 injections into the same site of the NTS. 6. ATP may function as a fast-acting neurotransmitter in the baroreceptor afferent pathway or in interneurons in the NTS. Adenosine is likely to play a role as a modulator of activity in baroreceptor and chemoreceptor pathways, fine tuning the functional output of both systems.