Adenosine is generally considered an inhibitory neuromodulator. It inhibits the release of many neurotransmitters and reduces neural activity. The stimulatory effects of caffeine may be at least partially explained by antagonism of adenosine. The overall aim of this research proposal is to examine the effect of adenosine on neural mechanisms that regulate blood pressure. These mechanisms are activated by stimulation of either mechano- or chemoreceptors (afferent limb). These signals are then integrated in the brainstem, where sympathetic discharge (efferent limb) is modulated. Adenosine may thus interact with neural cardiovascular control at multiple levels: 1) In the efferent limb, adenosine inhibits the release of norepinephrine from sympathetic nerve terminals, probably through pre- synaptic receptors. 2) In the brainstem, adenosine lowers blood pressure and inhibits sympathetic tone by acting in discrete nuclei. 3) In the afferent limb, recent evidence suggests that adenosine can stimulate sympathetic tone by activating sympathetic afferents. We will examine these last two effects in this proposal. The activation by adenosine of sympathetic afferents which increase blood pressure is particularly intriguing since it would seem to oppose the prevalent notion of adenosine acting as an inhibitory neuromodulator. Recent evidence suggests that adenosine activates myocardial and renal sympathetic afferents and arterial chemoreceptors. These findings raise the possibility that activation of sympathetic afferents by adenosine is actually a generalized rather than an isolated phenomena. However, little is known about the relevance and mechanism of this apparent activation of sympathetic afferents by adenosine. Therefore, this problem will be addressed by direct measurements of sympathetic nerve traffic in man. Evidence will also be presented that in the nucleus tractus solitarii of the brainstem, adenosine and glutamate have similar actions, and may actually interact to reduce blood pressure. This is also an unexpected finding since adenosine, in general, has opposing actions to those of the excitatory amino acid glutamate elsewhere in the CNS. It is this interaction as well as the relevance of adenosine to cardiovascular control in the brainstem that will be studied. We believe that the studies proposed will provide new information on endogenous mechanisms of blood pressure regulation in man.
| Braren, V; West Jr, J C; Boerth, R C et al. (1988) Management of children with hypertension from reflux or obstructive nephropathy. Urology 32:228-34 |
